Uterine Leiomyosarcoma Presenting as Breast Metastasis

A 74-year-old woman presented with a 5 mm hypoechoic solid mass in the left breast on routine mammographic screening. BIRAD score was 4b, suspicious for carcinoma by radiology. A stereotactic core biopsy was performed. It showed an atypical spindle cell neoplasm in a collagenous background. No in situ component was seen. The neoplastic cells had oval to spindle, moderately pleomorphic nuclei, irregular nuclear contours, and moderate eosinophilic cytoplasm (Fig. 1a). Mitoses were common including atypical forms. The differential diagnosis included spindle cell carcinoma, malignant phyllodes tumor, nodular fasciitis, and myofibroblastoma. Immunohistochemically the neoplastic cells were negative for pankeratin, Keratin 5/6, Keratin 903, ER, PR, CD34, S100, Mart1, and smooth muscle actin (SMA). The tumor cells were focally P63 positive (Fig. 1b). There was no Her-2/neu overexpression. Ki-67 was ~20%. A diagnosis of “Malignant spindle cell neoplasm, most consistent with metaplastic carcinoma, spindle cell type” was made. The patient subsequently underwent lumpectomy with sentinel lymph node dissection. No residual invasive carcinoma was found. Three sentinel lymph nodes were negative for metastatic carcinoma. Although advised to undergo radiation followed by chemotherapy, the patient decided to undergo radiation alone. Two months after completion of radiation therapy, she developed abdominal pain. Clinical work up included a transvaginal pelvic ultrasound. It showed an enlarged uterus, consistent with multiple myomas. CT of the abdomen and pelvis showed a large pelvic mass. An ultrasound guided biopsy was performed. Core biopsy sections of the pelvic mass showed mild to moderately atypical spindle cells with areas of necrosis. Occasional mitotic figures were seen. Immunohistochemical staining showed that the neoplastic cells were positive for desmin, smooth muscle actin, vimentin, focally positive for p63 and negative for pankeratin, Keratin 5/6, 34betaE12, CD10, CD34, CD117, S100, Mart1, and muscle-specific actin. Ki-67 was approximately 15%. Based on these findings, the diagnosis was “spindle cell neoplasm, favor low grade smooth muscle tumor”, with a comment that the presence of nuclear atypia and necrosis raised the possibility of a malignant process; but the biopsy was too small for a definitive diagnosis. CT scan of the chest was also performed and showed multiple pulmonary nodules. A CT-guided lung biopsy was performed. Core biopsy sections showed a spindle cell neoplasm with moderate to severe nuclear atypia, areas of necrosis, and frequent mitosis (four in one HPF). The morphological features were similar to that of the breast and pelvic tumor, but with a greater degree of nuclear atypia and mitotic activity. The neoplastic cells were strongly positive for desmin, vimentin, and smooth muscle actin and focal weak positive for p63. Additional immunostains performed on the breast biopsy showed a similar immunohistochemical profile as that of the pelvic tumor and lung nodules: positive for vimentin, smooth muscle actin (SMA) (Fig. 1c), desmin (Fig. 1d), and focal positivity for p63. Therefore, the diagnosis of a primary uterine leiomyosarcoma with metastasis to the lung and breast was made. Because of extensive pelvic disease as well as multiple metastatic lung lesions, she was referred for conservative medical treatment. Breast metastases from leiomyosarcoma are extremely rare. Usually, history is helpful in arriving at the correct diagnosis. In our case, the breast tumor was the initial presentation, making the diagnosis very difficult. The histologic differential diagnosis includes the following: spindle cell carcinoma, malignant phyllodes tumor with stromal overgrowth, nodular fasciitis, mammary fibromatosis, myofibroblastoma, solitary fibrous tumor, primary or metastatic sarcoma, and metastatic melanoma. Clinical and radiologic correlation is important. Careful morphological evaluation and an adequate panel of immunostains including a broad spectrum of keratins, actin, desmin, caldesmon, and S100 are important in making the correct diagnosis.