A 49-year-old African American woman presented with a palpable lump in the left breast at the 5-o'clock position. Ultrasound of the palpable area demonstrated a single 3.2-cm complex hypoechoic, partially shadowing lobulated and irregular solid mass, which was partially imaged mammographically because of its far posterior location. A chest radiograph and bone scan did not reveal any metastatic disease. A fine-needle aspiration biopsy of the mass was performed followed by a lumpectomy with lymph node sampling. Grossly, the lumpectomy specimen revealed a 4.3-cm, firm, gray-white mass with small foci of myxoid or gelatinous stroma. The patient received chemotherapy for approximately 6 to 7 months and radiation therapy to her breast. One year later, she developed shortness of breath and was found to have multiple lung metastases, bilateral pleural effusions, and an enlarged right supraclavicular lymph node. A fine-needle aspiration biopsy of the supraclavicular node and cytologic examination of the subsequent pleural effusion were positive for tumor cells.
Fine-needle aspiration biopsy of the breast mass revealed a cellular aspirate with dyscohesive tumor cells with high nucleus-to-cytoplasm ratio and pleomorphic nuclei. Fragments of metachromatic chondromyxoid extracellular material contained cells that were reminiscent of chondrocytes (Figure 1). Histopathology of the excised tumor revealed a poorly differentiated neoplasm composed mostly of solid sheets of small undifferentiated cells with frequent mitoses and foci of necrosis (Figure 2). Interspersed with the tumor cells were sharply delineated areas of chondromyxoid matrix containing cellular areas of pleomorphic cells within lacunae without an intervening spindle cell zone (Figure 3). The cellular component of these chondromyxoid areas was strongly positive with keratin and S100 protein (Figure 4).
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Pathologic Diagnosis: Matrix-Producing Metaplastic Carcinoma of the Breast
Matrix-producing carcinoma is a variant of heterologous metaplastic carcinoma of the breast that is composed of “overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix without either an intervening spindle cell zone or osteoclastic giant cells.”1 Generally, the age range at diagnosis (average age 58 years) and the clinical features of metaplastic mammary carcinomas are not appreciably different from those of other invasive mammary carcinomas.1,2 Patients typically present with a palpable mass of short duration and rapid growth.2 There are no features specific to the mammographic appearance of metaplastic carcinoma. The reported sizes of metaplastic mammary carcinoma range from 1 to 21 cm.3 The mean or median size (3 cm to 4 cm) reported in various series tends to be greater than that of usual carcinomas. The majority of tumors are described as firm to hard, nodular, and circumscribed, but some lesions have infiltrative borders.4
Microscopically, the carcinomatous element is composed of moderately to poorly differentiated adenocarcinoma with infrequent foci of squamous or apocrine metaplasia. Some tumors exhibit components of mucinous differentiation.4 The direct transition to a cartilaginous stromal matrix without an intervening spindle cell zone is a distinctive characteristic of these tumors.1 The cartilage-producing cells are negative for mucin, and the cartilaginous matrix has histochemical properties of a sulfated acid mucopolysaccharide consistent with chondroitin sulfate. The carcinoma cells outside the heterologous component stain positively with keratin, epithelial membrane antigen, and S100, with virtually no reactivity for vimentin. On the other hand, metaplastic cells in the cartilaginous matrix stain diffusely with S100 and vimentin, whereas staining with keratin and epithelial membrane antigen is variable. Ultrastructural examination and immunohistochemical evaluation reveal matrix-producing carcinoma to have myoepithelial characteristics.1 Regional lymph node as well as distant metastases may exhibit the same matrix-producing pattern as the primary tumor. Treatment for matrix-producing carcinoma is either mastectomy or local excision.
In a study of 26 such patients, Wargotz and Norris1 concluded that radiation and chemotherapy were of limited effectiveness. The 5-year survival rate for patients following mastectomy or partial mastectomy was 70%, contrasted with 50% for patients treated by local excision. The cumulative 5-year survival rate was 68%.1 One of 17 (6%) patients with axillary lymph node sampling had metastasis. Nine patients (35%) developed recurrent disease within 2.5 years, and 8 of these patients (89%) died from tumor within 4 years of initial therapy.1 Significant features of the tumors associated with progression were large size, diffuse cellularity of the stromal matrix, and atypical cartilaginous metaplasia.
In this case, the patient had a large tumor with high-grade cytology, mitoses, necrosis, and axillary node metastasis with extranodal extension at the time of diagnosis. The cartilaginous matrix had the appearance of chondrosarcoma, which was also evident in the metastatic lymph nodes (both axillary and supraclavicular lymph nodes). Despite surgery, radiotherapy, and adjuvant chemotherapy, the patient developed widespread metastases and died of disease 14 months after the diagnosis.
In conclusion, matrix-producing carcinoma is an aggressive form of metaplastic breast carcinoma that is not responsive to standard chemotherapy employed for breast carcinomas. Although it is rare, the differential diagnosis includes metastatic chondrosarcoma. The diagnosis of matrix-producing carcinoma can be considered on fine-needle aspiration biopsy material from primary or metastatic sites when metaplastic chondromyxoid matrix and distinct adenocarcinoma components are present.
References
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Corresponding author: Sunati Sahoo, MD, Department of Pathology, The University of Chicago, 5841 S Maryland Ave, MC 6101, Chicago, IL 60615 ([email protected]).