Case 3 -
Malignant Adenomyoepithelioma of Breast, Metastatic to the Lung and Kidney
National Institutes of Health
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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
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.
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.
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.
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
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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