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Lymphoepithelioma-like carcinoma of the breast is a rare malignancy, with fewer than 20 cases documented in the literature. Given the paucity of reported cases, there is limited information available to guide the diagnosis and management of patients with this tumor. We present a case of a 39-year-old woman with a palpable right breast mass that was initially diagnosed by core needle biopsy as infiltrating carcinoma with prominent lymphoplasmacytic stroma. Subsequent neoadjuvant chemotherapy with docetaxel, doxorubicin, and cyclophosphamide resulted in a marked decrease in the size of the mass. After wide local surgical excision, pathology revealed a lymphoepithelioma-like carcinoma of the breast. Given the excellent treatment response, our experience may help clinicians determine future therapeutic strategies for this rare breast tumor.
A 39-year-old Hispanic female presented to our breast clinic with a 2.5-year history of a right breast lump that had been gradually increasing in size. The patient did not have associated breast pain, skin changes, nipple discharge, or a history of breast trauma. Her past medical history was significant only for hypercholesterolemia. Her menarche was at age 13, and she was gravida 2 para 1, with one miscarriage. She was 20 years old at the time of her first birth. There was no family history of breast or ovarian cancer.
Her physical exam was notable for a palpable right breast mass located in the upper inner quadrant at the 1 o'clock position, measuring approximately 2 × 3 cm. No skin changes were visualized. The left breast exam was negative. There was no palpable lymphadenopathy in the axillary or the supraclavicular regions.
A diagnostic mammogram, subsequently performed, revealed a 2.7-cm, irregular-shaped, high-density mass with microlobulated margins at the 1 o'clock position (Fig. 1). Right breast ultrasound demonstrated a corresponding 2.7 × 2.5 × 2.5-cm, nonparallel, irregular-shaped, hypoechoic mass with heterogeneous internal echogenicity, microlobulated margins, and posterior acoustic enhancement (Fig. 2). The mass was categorized as Breast Imaging Reporting and Data System (BI-RADS) Category 4C: high suspicion for malignancy. The right axilla was sonographically negative for lymphadenopathy.
An ultrasound-guided, 14-gauge core-needle biopsy was performed, with the histologic result of infiltrating carcinoma with prominent lymphoplasmacytic stroma. The tumor was 40% positive for estrogen-receptor (ER), <1% positive for progesterone-receptor (PR), and HER2/neu was negative by fluorescence in-situ hybridization (FISH) testing. A BRST-2 stain showed rare positive cells, which favored a primary breast carcinoma; however, clinical correlation and metastatic workup to exclude a primary cancer elsewhere was recommended by pathology.
Computed tomography performed for cancer staging demonstrated an irregular-shaped, heterogeneously enhancing, soft-tissue-density mass in the right breast (Fig. 3) with no evidence of metastatic disease. The patient was referred for a genetic consultation and tested negative for the BRCA1/2 gene mutation.
Neoadjuvant chemotherapy with six cycles of docetaxel, doxorubicin, and cyclophosphamide was administered. Following completion of the neoadjuvant chemotherapy regimen, the breast mass was no longer palpable on physical exam. Only a small residual area of hypoechogenicity could be seen on a subsequent ultrasound examination, indicating an excellent treatment response (Fig. 4). Surgical therapy consisted of a needle-localized wide local excision and a sentinel lymph-node biopsy.
The right breast wide local excision specimen showed one small nodular focus of residual tumor measuring 4 mm. Microscopic examination revealed poorly defined nests and cords of undifferentiated epithelial cells with a prominent lymphoplasmacytic infiltrate (Figs. 5A, B). Immunohistochemical staining of the neoplastic cells demonstrated positivity for epithelial markers CAM 5.2 (Fig. 5C), HMW, and CK7. These cells were negative for Epstein-Barr virus Latent Membrane Protein. The lymphocytes were predominantly CD3-positive (Fig. 5D) with focal CD20 positivity. These findings, including the morphology and immunohistochemical staining profile, were consistent with the diagnosis of lymphoepithelioma-like carcinoma of the breast.
Five out of five sentinel lymph nodes removed were negative for tumor involvement. Final staging was ypT1aN0M0, Stage IA. Postoperative adjuvant radiation therapy was administered. Given the ER-positive tumor and premenopausal status of the patient, antihormonal therapy with tamoxifen was also initiated. To date, there is no evidence of local or distant recurrence after 2 years of followup.
Lymphoepithelioma-like carcinoma (LELC) is a malignancy that microscopically resembles nasopharyngeal lymphoepithelioma. While LELC can occur in many organ systems, this entity rarely occurs in the breast. Kumar and Kumar (1) published the first instance of LELC of the breast in 1994, and since then fewer than 20 cases of this tumor have been documented in the literature (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13). The age of initial presentation of the previous cases ranged from 37 to 69 years (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13). At this time, the etiology of LELC of the breast remains unknown. LELC tumor cells in other organ systems have been associated with varying degrees of Epstein-Barr virus (EBV) genome expression; however, there have been no documented cases of EBV detected in LELC of the breast (2).
The clinical and imaging findings of LELC of the breast are similar to that of other primary breast malignancies. Clinically, LELC of the breast often presents as a palpable breast mass. The mammogram may show a high-density, irregular-shaped mass with microlobulated margins, a circumscribed mass, or a poorly defined mass that can appear mammographically as a focal asymmetry (3, 4). Sonographic evaluation may demonstrate a solid hypoechoic mass with microlobulated margins and posterior acoustic enhancement, or an area of subtle abnormal parenchyma (4, 5). Computed tomography may reveal a heterogeneously enhancing or low-density mass (6). Previously documented tumor sizes ranged from 1 cm to 4 cm at the time of diagnosis. Four prior cases have noted metastatic lymph-node involvement; therefore, thorough examination of the axillary and supraclavicular regions is important to identify potential lymphadenopathy (6).
The differential diagnosis of LELC of the breast based on clinical and imaging findings includes primary invasive breast cancers, metastasis, and lymphoma (Table 1). Once tissue has been obtained, the differential diagnoses are usually narrowed to lymphoma and medullary carcinoma. Histologically, LELC of the breast can appear similar to lymphoma due to the presence of undifferentiated cancer cells surrounded by a prominent lymphocytic infiltrate. Medullary carcinoma is also a consideration, because LELC of the breast shares a similar cellular morphology. Application of immunohistochemistry and careful investigation of the tissue architecture are helpful in distinguishing these entities (6).
Since LELC of the breast is so rare, limited information is available to direct optimal oncologic management. All reported instances in the literature have been treated surgically, either with wide local excision or mastectomy, and with or without adjuvant radiotherapy. Chemotherapy had been used in three previous cases; however, only one therapeutic regimen has been described in the literature (cyclophosphamide, epirubicin, and 5-fluorouracil), and this was administered only after the patient presented with chest-wall recurrence (5, 7, 8). This patient later developed lung metastasis (7). One patient was found to have developed LELC of the contralateral breast three years after the initial diagnosis. The remaining cases demonstrated no evidence of disease at the time of followup (range: 3–72 months).
To our knowledge, there has been no documented use of neoadjuvant chemotherapy prior to surgical treatment of LELC of the breast. Our case demonstrated excellent treatment response to a neoadjuvant chemotherapy regimen of docetaxel, doxorubicin, and cyclophosphamide prior to breast-conserving surgical excision. Given the paucity of previous cases to guide physicians encountering this entity, our experience may help facilitate future management decisions.
Published: February 27, 2015