—  SPECIALTY CONFERENCE  —

Surgical Pathology

Case 3 - Malignant Adenomyoepithelioma of Breast, Metastatic to the Lung and Kidney

Maria Merino
National Institutes of Health
Bethesda, Maryland


Click on each slide thumbnail image for an enlarged view
Clinical History:
A 52-year-old woman was referred to the NCI for a phase I protocol trial with the diagnosis of advanced sarcomatoid renal cell carcinoma. Past medical history included breast cancer ten years prior to admission, and lung cancer four years later. Both tumors had been interpreted as separate primaries; infiltrating ductal carcinoma of breast, and a primary bronchoalveolar carcinoma of the lung. Two years later, the patient presented with hematuria. CT scans revealed a mass in the right kidney. A right nephrectomy was performed and a renal cell carcinoma, sarcomatoid variant, was diagnosed. A few months later, a CAT scan showed a 1.5 x 1.0-cm lesion in the left lung base. A needle biopsy disclosed a high-grade adenocarcinoma, favoring metastases from the lung or kidney. Thoracotomy and wedge resection was performed and the pathology diagnosis was high-grade adenocarcinoma that was estrogen and progesterone receptor negative. The patient was treated with interleukin-2 and alpha interferon for four weeks. On reevaluation, a CAT scan demonstrated multiple masses in the left kidney, the largest measuring 2 cm, and a left apical lung mass that was 2.5 x 3.5 cm. A PET scan revealed positive uptake in these areas. A CT-directed biopsy of the kidney revealed cellular oncocytic aggregates suspicious for renal cell carcinoma. She then was referred for possible participation on a Phase I study at the NIH clinic.


Case 3 - Figure 1 - Scanning magnification showing fibrous connective tissue overrun by sheets of atypical tumor cells with extensive areas of necrosis.
Case 3 - Figure 2 - Poorly-differentiated tumor cells are seen entrapping nerves.
Case 3 - Figure 3 - Higher magnification shows atypical, round to oval tumor cells with small nucleoli.

Pathologic Findings:

Breast:
A modified radical mastectomy had been performed, revealing a tumor that measured 3.8 cm in greatest dimension with ill-defined margins. Areas of fibrosis and necrosis were pressent. In addition multiple cysts of varying sizes measuring up to 1.0 cm were noted in the remaining breast parenchyma. Thirteen axillary lymph nodes were negative for tumor. Histologically, the tumor was composed of a mixture of malignant epithelial cells arranged in cords and tubule-like structures. The ducts were surrounded by prominent spindle myoepithelial cells with high nuclear/cytoplasm ratio showing occasional clearing of the cytoplasm. In-situ ductal carcinoma, high-grade, as well as apocrine metaplasia and sclerosing adenosis were also noted. Mitotic figures were observed. The reviewed diagnosis was that of malignant adenomyoepithelioma. The myoepithelial components were positive for S100, SMA, calponin and cytokeratin, and focally positive for EMA.

Lung:
The first lung wedge biopsy performed six years after the breast tumor showed a single nodule in the left upper lobe measuring about 1.3 cm in diameter. Microscopically, the metastasis showed a mixture of epithelial and myoepithelial cells, with the myoepithelial cells having similar histological pattern and cellular appearance to the breast lesion. The epithelial cells, however, represented remnants of trapped bronchial epithelium, giving the impression of a bronchoalveolar carcinoma. The immunostain of the myoepithelial cells were also positive for SMA and S100, similar to that of the breast lesion, supporting the diagnosis of metastatic malignant adenomyoepithelioma.

Kidney:
The right nephrectomy revealed a mass occupying 75% of the renal parenchyma, weighing 506 grams and measuring 14 x 7 x 5 cm. There was no gross involvement of vascular and ureteral margins. Histologically, the tumor in the kidney showed areas of sarcomatoid changes with resemblance to the myoepithelial lesions seen in the breast and lung. Focal glandular structures as well as prominent myoepithelial cells were present. Focally, the spindle myoepithelial component was difficult to differentiate from renal cell carcinoma, sarcomatoid variant. The immunohistochemical stains revealed that the tumor cells were still positive for SMA and somewhat reduced in reactivity for S100 staining, suggesting it was most likely a metastasis from the malignant adenomyoepithelioma of the breast.

Diagnosis - Malignant Adenomyoepithelioma of Breast, Metastatic to the Lung and Kidney

Discussion:
Hamperl in 1970 described the first adenomyoepithelial lesion in the mammary gland, and coined the term "adeno-myoepithelioma" to describe tumors in which two cell populations, epithelial and myoepithelial were clearly identified. He described and illustrated a single case of adenomyoepithelioma. In the early 1990s, adenomyoepithelioma was subclassified into spindle cell, tubular, and lobulated variants based on their growth pattern and cell type by the AFIP.

The spindle-cell type was defined as a tumor composed predominantly of spindle myoepithelial cells admixed with few epithelial-lined spaces. The tubular type showed a characteristic proliferation of rounded tubules lined by both epithelial and myoepithelial cells. The third variant, the lobulated adenomyoepithelioma, consisted of solid nests of clear, eosinophilic or hyaline myoepithelial cells compressing epithelial-lined spaces. The distinction between benign and malignant lesions is difficult and may reside in the presence of distant metastases. Suggested histological features helpful to differentiate malignant from benign adenomyoepithelioma include the presence of mitoses, pleomorphism, necrosis, high cellularity, infiltration of surrounding tissues, presence of satellite foci, and predominance of myoepithelial cells.

The differential diagnosis of MAM should include other stromal proliferations and malignant tumors such as Fibromatosis and Spindle cell Carcinoma

Spindle cell carcinomas , or carcinomas with a pseudosarcomatous appearance, are well known to occur in other sites such as the skin, upper respiratory tract, and esophagus. Bauer et al. reviewed the literature and identified 42 cases, 3 of which were incompletely documented.

Microscopically, the hallmark of these neoplasms is the presence of a biphasic tumor with prominent pseudosarcomatous stroma made of spindle cells, blending with nests of malignant epithelium such as squamous cell carcinoma or adenocarcinoma. The sarcoma-like areas are composed of spindle cells that diffusely infiltrate and destroye the adjacent normal breast parenchyma. The cells have round- to oval-shaped nuclei, and variable amounts of interstitial collagen separating the spindle cells in a pattern similar to that seen in fibrosarcomas. The margins of the tumor are poorly circumscribed and infiltrative, with tumor cells percolating into the adipose tissue and trapping normal mammary ducts in a manner commonly seen in cystosarcoma phyllodes.

Fibromatosis is predominantly a paucicellular growth with infiltrative borders. The cells are spindled with regular nuclei and lacking significant atypia. These cells can occasionally be positive for SMA since they are of myofibroblastic derivation.

The diagnosis of malignant adenomyoepithelioma in the present case is based on the fact that the original breast lesion had two different components, namely, epithelial and myoepithelial cells, that showed malignant features including atypia, high cellularity. The evidence to support the notion of a single primary tumor which metastasize to lung and kidney rather than second or third primary tumor is based on the similar histology and immunohistochemical staining patterns among the tumors in all three sites. The histological appearance of the lung metastasis mimicked a primary bronchoalveolar carcinoma of the lung And the renal tumor closely resemble renal cell carcinoma with sarcomatoid differentiation. However, their immunoreactivity to S100 and smooth muscle actin antibodies strongly support the diagnosis of metastasis of malignant adenomyoepithelioma . The patient is receiving adjuvant chemotherapy but metastasis persist.

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