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Metastases to Breast from Primary Lung Cancer

      Abstract

      Metastatic disease to the breast from extra mammary sites is uncommon and has an incidence of 0.5 to 3%. It is important to make an accurate diagnosis as this has an impact on the therapeutic planning and management. Clinically, it can be difficult to differentiate between primary breast cancer and a metastatic disease. An incorrect diagnosis can lead to unnecessary surgical interventions. Immunohistochemistry has a significant role in identifying the primary origin of tumor and has to be considered in the presence of unusual cytologic patterns. We report three cases of metastatic disease to breast from primary lung tumors. The cases demonstrate the difficulties encountered in the diagnosis and the impact on the management of these patients.

      Key Words

      Breast is an unusual site for metastases particularly from primary lung cancer. Metastases to the breast from nonmammary malignant neoplasms are rare and an autopsy series showed that metastases accounted for 0.5 to 6.6% of all breast malignancies.
      • Amichetti M
      • Perani B
      • Boi S
      Metastases to the breast from extramammary malignancies.
      • Bohman LG
      • Bassett LW
      • Gold RH
      • et al.
      Breast metastases from extramammary malignancies.
      Metastatic spread to the breast has an incidence of 0.5 to 3% from extramammary sites.
      • Abrams HL
      • Spiro R
      • Goldstein N
      Metastases in carcinoma; analysis of 1000 autopsied cases.
      • McCrea ES
      • Johnston C
      • Haney PJ
      Metastases to the breast.
      We report three unusual cases of metastases to the breast from primary lung cancer.

      Case I

      A 51-year-old smoker with a 30 pack year history was referred to the breast surgeons for an enlarging lump in the axillary tail of her left breast. The lump exhibited skin tethering and was suspicious of primary breast malignancy. Mammography demonstrated a radiologically malignant ill-defined rounded mass lesion in the left upper outer quadrant, fine-needle aspiration of which revealed malignant cells. A chest radiograph was normal. She underwent ultrasound guided core biopsy of the left breast. Histopathological examination of this core demonstrated an infiltrating carcinoma consistent with an origin in breast which was confirmed by a trucut biopsy (Figure 1). She therefore underwent wide local excision and axillary node clearance. Histopathological examination of this specimen showed grade 3, node negative carcinoma of no special type. The tumor was estrogen receptor (ER), progesterone receptor (PR) and Herceptin negative.
      Figure thumbnail gr1
      FIGURE 1Trucut biopsy of breast lump shows sheets of pleomorphic cells with a moderate amount of cytoplasm consistent with poorly differentiated carcinoma (hematoxylin-eosin, ×200).
      A month after excision of the breast mass the patient developed subcutaneous lumps in her abdominal wall and right thigh. Mediastinal adenopathy was evident on the computed tomography (CT) scan of the thorax, abdomen, and pelvis (Figure 2). There were multiple small opacities in both lungs measuring up to 6 mm suggestive of pulmonary metastases. There was also a 6 mm subcutaneous deposit in the medial aspect of her right breast that was consistent with a skin deposit with a further 9 mm lesion noted in the abdominal wall, and a 13 mm right posterior thigh nodule. The radiologic picture was felt to be less likely to represent metastatic breast cancer. She therefore underwent trucut biopsy of the nodules from the abdominal wall and thigh. Histopathological examination of both biopsies showed invasive adenocarcinoma which with immunohistochemical staining, were strongly positive for CK7 and TTF1 but negative for ER and PR. In retrospect, immunohistochemistry of the resected breast tissue also confirmed widespread nuclear positivity of the specimen to TTF1 (Figure 3). This lady was treated with platinum based chemotherapy for stage IV non-small cell lung cancer and is currently under follow-up at the time of writing this report.
      Figure thumbnail gr2
      FIGURE 2Computed tomography (CT) scan of the thorax, abdomen, and pelvis showed evidence of extensive mediastinal lymphadenopathy, predominantly in the right hilar, precarinal, and pretracheal regions.
      Figure thumbnail gr3
      FIGURE 3Immunohistochemical staining of resected breast tissue shows widespread nuclear positivity for TTF-1 (TTF-1, ×200).

      Case II

      A 69-year-old woman was admitted with breathlessness, chest pain, and a breast lump. She was a smoker and had a background of atrial fibrillation, chronic obstructive pulmonary disease, and hypertension. Clinical examination revealed a 4 × 2 cm hard mass in the right breast. A right sided rounded opacity was seen on her chest radiograph. She underwent a CT of chest and abdomen which demonstrated two nodules in the right lung, the largest of which measured 2 cm in diameter with a right breast mass (Figure 4). There was a mediastinal mass encasing both main stem bronchi and a right axillary node. Below the diaphragm there were ring enhancing lesions in both lobes of the liver, and a soft tissue lesion in the right arm consistent with metastases.
      Figure thumbnail gr4
      FIGURE 4Computed tomography (CT) of chest showing the right breast mass (arrow) and extensive mediastinal adenopathy.
      She underwent core biopsy of the breast mass and histopathological examination showed a small cell carcinoma confirmed by immunohistochemical staining showing strong positive staining for TTF1 with dot type positivity for AE1/3 and strong membranous positivity for CD 56. In view of her poor performance status she was deemed not fit for systemic treatment and she died in the hospital.

      Case III

      An 82-year-old woman smoker with a background of chronic obstructive pulmonary disease was admitted with increasing breathlessness. Clinical examination revealed a left sided 2 × 2 cm, hard and fixed breast lump, and signs of a right sided effusion with no evidence of lymphadenopathy. Chest radiograph demonstrated right middle and lower lobe consolidation and fluid. CT scan of the chest confirmed the clinical impression of a malignant left breast mass with extensive mediastinal and right hilar lymphadenopathy, few intrapulmonary nodules, right middle and lower lobe consolidation with right pleural effusion, and a small stellate opacity in the left upper lobe. There were also widespread hepatic and probable spleenic metastases. Histopathological examination of a core biopsy of the breast mass showed an infiltrating poorly differentiated carcinoma consistent with primary breast origin. However, immunohistochemical staining showed the tumor to be ER/PR, Hercept test negative and TTF1, CD56, and P63 positive in keeping with a large cell neuroendocrine carcinoma of lung. This patient underwent palliative radiotherapy but died a few weeks later.

      DISCUSSION

      Metastatic cancer is an unexpected diagnosis in a female patient presenting with a breast mass and is relatively uncommon due to large area of fibrous tissue and relatively poor blood supply of the breast.
      • Yeh CN
      • Lin CH
      • Chen MF
      Clinical and ultrasonographic characteristics of breast metastases from extramammary malignancies.
      The commonest cause is spread from a contralateral primary breast carcinoma.
      • Akcay MN
      Metastatic disease in the breast.
      The most common primary tumors metastasizing to the breast include melanoma and lymphoma.
      • Bassi F
      • Gatti G
      • Mauri E
      • et al.
      Breast metastases from cutaneous malignant melanoma.
      Lung, ovarian cancer, and soft tissue tumors uncommonly metastasize to the breast.
      • Vizcaino I
      • Torregrosa A
      • Higueras V
      • et al.
      Metastasis to the breast from extramammary malignancies: a report of four cases and a review of literature.
      Although the typical presentation of primary breast cancers include pain, tenderness and nipple discharge, metastases to the breast from extramammary sites usually present as solitary breast masses.
      In most situations, metastatic disease to the breast occurs after the diagnosis of the primary tumor. In approximately 25% of patients, a breast mass is the cause for the initial presentation. In these patients, metastases to the breast can mimic benign disease or primary breast malignancies.
      • Gupta D
      • Merino MI
      • Farhood A
      • et al.
      Metastases to breast simulating ductal carcinoma in situ: report of two cases and review of the literature.
      In all of these three cases, a breast mass was the initial mode of presentation.
      Most metastatic breast masses present as palpable painless lumps and skin tethering is uncommon. One of our patients (case I) had skin tethering making the diagnosis of metastasis in the breast extremely unlikely. Diffuse skin involvement, however, has been reported with melanoma metastasizing to the breast.
      • Hebert G
      • Ouimet-Oliva D
      • Paquin F
      • et al.
      Diffuse metastatic involvement of the breast.
      Clinically, it can be difficult to differentiate between primary cancers that metastasize to the breast and primary breast carcinomas. Metastases to the breast typically lie in the subcutaneous plane and hence are usually palpable. Primary breast carcinomas arise from the glandular epithelium and are usually deep seated but also often palpable.
      • Noguera JJ
      • Martinez-Miravete P
      • Idoate F
      • et al.
      Metastases to the breast: a review of 33 cases.
      In all our cases the breast lump was palpable.
      Mammography usually reveals a well defined rounded mass and multiple or bilateral lesions are seen in a minority of cases.
      • Noguera JJ
      • Martinez-Miravete P
      • Idoate F
      • et al.
      Metastases to the breast: a review of 33 cases.
      In contrast with primary breast cancers, calcification is rare and speculation uncommon.
      • Vergier B
      • Trojani M
      • de Mascarel I
      • et al.
      Metastases to the breast: differential diagnosis from primary breast carcinoma.
      Breast masses presenting as metastatic spread from primary lung cancer can be difficult to diagnose in the absence of new and concerning respiratory symptoms (e.g., cough, hemoptysis). Histopathology can provide the diagnosis. However in most instances immunohistochemical staining is required to confirm the primary site of the tumor as evidenced in case I.
      The outcome for this group of patients is poor and 80% of patients with breast metastases arising from lung die within 1 year of presentation.
      • Sneige N
      • Zachariah S
      • Fanning TV
      • et al.
      Fine-needle aspiration cytology of metastatic neoplasms in the breast.
      In our series, two patients had died by the time of reporting and case I had received chemotherapy.
      Metastatic masses in the breast are uncommon with the commonest reported source being from a melanoma primary. Lung cancer presenting as a metastasis in the breast is uncommon. It is important to consider this possibility, particularly in smokers, to avoid an incorrect diagnosis and unnecessary surgery and in this regard, immunohistochemistry is essential.

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