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Invasive Carcinoma III - Breast
IV. SPECIAL VARIANTS OF INFILTRATING DUCTAL CARCINOMA
A. Tubular Carcinoma
Tubular carcinoma represents an extremely well differentiated form of infiltrating ductal carcinoma usually less than 2 cm in dimension. Most if not all tumor cells form regular or sometimes angulated tubular glands surrounded by desmoplastic stroma and elastosis (Slide 18). Infiltration into fat, when present, is indicative of invasive carcinoma (Slide 19). These glands are lined by a single layer of cells with mild nuclear atypia (Slide 20). Apocrine differentiation is commonly observed. In two-thirds of the cases, non-comedo, ductal carcinoma in situ is present (Slide 18).
Some authors require the "pure" tubular carcinoma to have at least 75% of tubular glands (Rosen and Oberman), others demand 100% tubular glands (Tavassoli). When the tubular component is less than 75% of the tumor, the tumor should be classified as mixed form of tubular carcinoma or conventional infiltrating ductal carcinoma.
Pure tubular carcinomas have an excellent prognosis, due to low rates of lymph node metastasis and recurrence following complete excision. The mixed form of tubular carcinoma is prognostically similar to infiltrating ductal carcinoma of comparable degree of differentiation and tumor size (McDivitt et al, Peters et al). Tubular carcinoma may be confused with sclerosing adenosis. Sclerosing adenosis maintains a lobular architecture and the glands, although distorted by fibrosis, are lined by double cell layers consisting of both epithelial and myoepithelial cells. In contrast, tubular carcinoma infiltrates locally without lobular pattern and the glands are lined by a single layer of tumor cells.
B. Mucinous Carcinoma
These tumors have lobulated borders, soft consistency and gelatinous cut surfaces, and may be confused with benign tumors, such as fibroadenoma.
Mucinous carcinoma is characterized by abundant extracellular mucin in which tumor cells form papillary clusters, glands and occasionally sheets (Slide 21). Individual cells have low grade nuclear atypia. Some cells have signet ring appearance.
The entire tumor or at least 75% of the tumor should contain mucinous area. Those invasive ductal carcinomas having less than 75% of mucinous component are best classified as mixed carcinoma, because of their less favorable outcome when compared to pure mucinous carcinoma.
C. Papillary Carcinoma
It typically occurs in the central portion of the breast as a round, 2-3 cm nodule with cystic change and hemorrhage.
It closely resembles papillary and cribriform ductal carcinoma in situ (Slide 22). Complex papillary projections and cribriform glands consist almost entirely of epithelial cells without myoepithelial cells. Fibrovascular stalks are less prominent than benign intraductal papilloma. The borders are irregular and infiltrative (Slide 23).
Tumor cells have low nuclear grade, inconspicuous nucleoli, and low mitotic activity.
Prognosis is excellent with low frequency of lymph node metastasis and tumor recurrence, if completely excised
D. Medullary Carcinoma
Medullary carcinoma can be quite large, soft on palpation, hemorrhagic and necrotic. Microscopically, medullary carcinoma should meet all of the following criteria: 1) smooth, non-infiltrative borders (Slide 24), 2) prominent lymphoplasmocytic infiltration present diffusely within the tumor and involving at least 75% of the tumor periphery, 3) tumor cells are arranged in large solid nests and sheets with poorly defined cell borders, the so-called syncytial pattern (Slide 25), 4) Individual cells have large pleomorphic nuclei, prominent nucleoli, and high mitotic activity, and 5) Fibrous stroma should be limited in amount. A small portion of the tumor may undergo squamous metaplasia or contains papillary, glandular elements.
Those tumors, having some but not all of the above mentioned features, are classified as "atypical" medullary carcinoma (Slide 26) or the usual variant of infiltrating ductal carcinoma. Using the above strict criteria, medullary carcinomas have better outcome than atypical medullary carcinoma or the conventional infiltrating ductal carcinoma, stage by stage (Wargotz and Silverberg). The survival rates for women with medullary carcinoma is 94%, as compared to 64% for those with atypical medullary carcinoma (Wargotz and Silverberg).
E. Metaplastic Carcinoma
It tends to be bulky and the tumor consists of poorly differentiated tumor cells undergoing squamous, spindle cell, and sarcomatoid metaplasias (Slides 27 and 28). In the latter, cartilaginous, osteoblastic and rhabdomyoblastic elements occur. The areas of poorly differentiated ductal carcinoma may be limited. Without immunohistochemical stains, spindle cell and sarcomatoid components are difficult to distinguish from fibrosarcoma, leiomyosarcoma, osteosarcoma, rhabdomyosarcoma, and metastatic tumors. By immunohistochemistry, expression of cytokeratin and other epithelial tumor antigens can be demonstrated to support the diagnosis of metaplastic carcinoma (Wargotz) (Slide 29). The overall prognosis is worse than conventional infiltrating ductal carcinoma.
F. Inflammatory Carcinoma
The clinical manifestation of diffuse thickening and edema involving at least one third of the mammary skin is essential for this diagnosis. The affected area is warm, erythematous with orange peel appearance.
Microscopically, inflammatory carcinomas are usually poorly differentiated with malignant cells filling the dermal lymphatic spaces. The surrounding dermis is edematous and infiltrated by lymphocytes (Slide 30). Recurrent carcinoma associated with inflammatory skin changes is referred to as secondary inflammatory carcinoma, in which case, nodules of malignant cells involve both the dermis and the lymphatic spaces. When these dermal changes are evident histologically, but not associated with typical clinical findings, the lesion is referred to as occult inflammatory carcinoma. Most studies have demonstrated poor outcome for patients with primary, secondary or occult inflammatory carcinoma.
G. Adenoid Cystic Carcinoma of the Breast
It has the same histologic appearance as that occurred in the salivary gland. Basaloid cells forming sieve-like cribriform spaces which contain mucinous material. A second feature is the deposit of basement membrane substance resulting in hyaline membranes and hyaline cylinders. Less commonly the tumor cells form tubules and solid sheets. The prognosis of women with adenoid cystic carcinoma is excellent following complete local excision. Axillary nodal metastasis rarely, if ever, occurs (Rosen 1989).
H. Microinvasive Carcinoma
The histologic criteria for the early, minimal invasive carcinoma of the breast have not been well defined. Some authors have limited this entity to early stromal invasion arising from the ducts and lobules involved by intraductal carcinoma with tongue-like processes (Slides 31 and 32). According to Tavassoli, the depth of invasion should be less than 1 mm measuring from the basement membrane and the diameter of the invasive foci to be less than 2 mm (Tavassoli). The optimal management of these cases remains controversial.
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