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Invasive Carcinoma IV - Breast

 

V. LOBULAR CARCINOMA IN SITU & INFILTRATING LOBULAR CARCINOMA


A. Lobular carcinoma in situ (LCIS)

LCIS was originally described in 1941 by Foote and Stewart. Most of these changes are found incidentally in specimens excised for benign or malignant diseases, because LCIS is not detectable by clinical and mammographic examinations. They may be multifocal, multicentric, or bilateral. LCIS is believed by most to be a high risk marker, rather than a true malignancy. As compared to general population, a woman with LCIS increases the relative risk of developing invasive carcinoma by eight to eleven times. The risk of developing invasive carcinoma is 20 to 25 percent at 15 to 20 years following biopsy (Haagensen, Rosen et al 1978). The invasive carcinoma may be ductal or lobular in type and may occur at any location in either breast.

The involved lobules and terminal ductules become distended and filled with homogeneous population of atypical cells which have relatively uniform round to oval, hyperchromatic nuclei, inconspicuous or small nucleoli, and low mitotic activity (Slide 33 and 34). The cytoplasm is scant to moderate in amount. Sometimes intracytoplasmic lumens are evident and contain mucinous material in the cytoplasm, a feature useful for diagnosis (Slides 35 and 36). The background myoepithelial cells have largely disappeared. The neoplastic cells proliferate and spread to the adjacent ducts in a pagetoid fashion between the epithelial and myoepithelial cells (Slide 37).

LCIS can be distinguished from ductal carcinoma in situ extending into lobules by having small to medium nuclear size, mild to moderate degree of nuclear irregularity, small nucleoli, and limited amount of cytoplasm. It should be mentioned that in excised specimens for LCIS, about 30% also have coexisting DCIS.

The risk for local recurrence of LCIS is directly related to the number of foci involved in the excised tissue.


B. Infiltrating Lobular Carcinoma

The gross appearance of infiltrating lobular carcinomas is similar to invasive ductal carcinoma presenting as an ill-defined, indurated, firm mass (Slide 38). However, because of a high propensity for multifocality and diffuse infiltration of the adjacent fibroadipose tissue, some neoplasms do not produce a discrete mass. The excised breast tissue may appear entirely normal, except for slight firmness on palpation (Slide 39).

In the tumor, in situ and infiltration lobular carcinoma sometimes coexist (Slide 40) About 85% of infiltrating lobular carcinomas are of the classic type and the remaining 15% special variants. In the classic type, the tumor cells spread between the collagen bundles in a single line, the so-called Indian file pattern (Slide 41). As the tumor cells spread around the periductal fibrous tissue concentrically, a targetoid pattern results (Slide 42). Individual cells have small to medium sized, uniformly round to oval nuclei, scant cytoplasm, inconspicuous nucleoli and low mitotic activity. The cytoplasm may contain intracytoplasmic lumen or accumulation of mucinous substance with a signet ring appearance (Slide 43). Sometimes the tumor cells appear so benign as to simulate mature lymphocytes.

Several variants of infiltrating lobular carcinoma have been recognized. In the solid type, the tumor cells appear in diffuse sheets with little intervening stroma to simulate malignant lymphoma or leukemic infiltration (Slide 44). In the alveolar variant, loosely cohesive tumor cells form discrete aggregates and are surrounded by fibrous stroma. The pleomorphic variant is made up of cells with medium to large, irregular, hyperchromatic nuclei and eosinophilic cytoplasm simulating rhabdomyoblasts (Slide 45) (Steinbrecher, DiCostanzo et al).

When compared stage by stage, stage I infiltrating lobular carcinoma patients have a higher disease-free survival than those with infiltrating ductal carcinoma (p = 0.02) (DiCostanzo et al). No difference is detected for stage II patients with infiltrating lobular or ductal carcinomas. Patients with classic infiltrating lobular carcinoma have a better prognosis than those with variants of lobular carcinoma (DiCostanzo et al).

 

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