When the diagnosis is restricted to the histologic and cytologic features of an invasive carcinoma, as described in the preceding paragraph, less than 5% of carcinomas qualify for the diagnosis of the classic type of ILC (1,2,3). If the classification is broadened to include variant forms, the frequency of ILC has reportedly been as high as 10% to 14% of all invasive carcinomas (4,5,6). ILC occurs almost throughout the entire age range of breast carcinoma in adult women (28-86 years). Most studies have placed the median age at diagnosis between 45 and 56 years (2,3,5,6,7). ILC is relatively more common among women older than 75 years (11%) than in women 35 years or younger. A population-based study of women with invasive breast carcinoma diagnosed from 1987 to 1999 revealed that the incidence rate of lobular carcinoma increased during this period (8). The increased incidence rate of ILC was greatest in women 50 years of age or older. On the other hand, the incidence rate for invasive ductal carcinoma (IDC) was relatively constant. In the absence of a systematic histopathologic review, these data have marginal reliability. ILC of classic as well as pleomorphic types occurs, albeit rarely, in the male breast (9,10,11,12).

The presenting symptom of ILC in almost all cases is either a mass or a radiologically evident lesion. In a minority of cases, the only physical evidence of the neoplasm is vague thickening or diffuse nodularity of the breast.

On mammography, ILC usually manifests as a spiculated mass or architectural distortion, and it is not prone to exhibit calcifications. Calcifications may be present coincidentally in benign proliferative lesions such as sclerosing adenosis associated with ILC (13). A lower frequency of calcifications detected by mammography has been reported in ILC than in ductal carcinomas (14,15,16). Exceptions are ILC arising in florid lobular carcinoma in situ (F-LCIS) or pleomorphic lobular carcinoma in situ (P-LCIS), both of which show central necrosis and calcifications within glands (see Chapter 18). In the screening setting, ILC is found more often clinically during intervals between examinations than by mammography (so-called “interval carcinomas”) (17). The mammographic size of ILC tends to be lesser when determined mammographically than grossly (18), although the latter methodology has its own disadvantages (19).

The most common mammographic manifestation of ILC is an asymmetric, ill-defined or irregular, spiculated mass (13,14,16,20). In one study, 46% of mammograms from patients who ultimately proved to have ILC were initially reported to be negative (15). The absence of well-defined margins and a tendency to form multiple subtle nodules of variable extent throughout the breast in some cases are features that hinder the radiologic detection of ILC and lead to a false-negative interpretation of mammograms. Patients with a spiculated ILC are less likely to have residual carcinoma when re-excision is performed than are those with ill-defined or asymmetric lesions (21). A minority of ILC present with mammographically round or ovoid tumors (22). In a radiologic study of 27 ILCs and 85 IDCs, “normal” findings and mass lesions on mammography and posterior acoustic shadowing on ultrasound evaluation were more frequently associated with ILC than with IDC (23).

Ultrasonography has been useful for detecting multifocal and multicentric ILC (24), and it may be more accurate than mammography for predicting tumor size (25). Selinko et al. (26) reported that the sensitivity of sonography for detecting ILC (98%) was substantially higher than the sensitivity of mammography (65%).

Rodenko et al. (27) found that magnetic resonance imaging (MRI) was more effective than mammography in a significant proportion of cases for determining the extent of a primary ILC, but the presence of metastatic carcinoma in axillary lymph nodes was not detected in four cases examined. Yeh et al. (28) reported that tumor morphology as seen on MRI combined with quantitative measurement of gadolinium uptake was effective for detecting ILC in most cases. However, in the absence of an enhancing mass, ILC may not be detectable by MRI. ILC enhances slower than IDC on MRI, but peak enhancement
is not significantly less (29). In the context of ILC, the effectiveness of MRI is somewhat diminished by the high rate of false-positives and overestimation of extent of disease limit.

Breast-specific gamma imaging (BSGI) has potential to be the most effective radiologic tool for the detection of ILC. In a study by Brem et al. (30), 26 women with a total of 28 biopsy-proven ILC, BSGI was shown to have the highest sensitivity for the detection of ILC with a sensitivity of 93%, whereas mammography, sonography, and MRI showed sensitivities of 79%, 68%, and 83%, respectively.

Patients with ILC are reported to have a relatively high frequency of bilateral carcinoma when compared with women who have other types of carcinoma (31,32,33). The reported relative risk for contralateral carcinoma in women with ILC when compared with those with ductal carcinoma ranged from 1.6 to 2 (34,35). Synchronous and metachronous contralateral carcinomas have been described in 6% to 28% of ILC cases (5,7,36). The reported incidence of subsequent contralateral carcinoma ranges from 1.0 (36,37) to 2.38 (38) per 100 women per year. There is some evidence that the frequency of bilaterality is higher in patients with classic ILC than in patients with the variant subtypes (38). A lobular component has been found in the majority of synchronous or metachronous contralateral carcinomas, and at least 50% of these have been invasive (7,36,37). In one series, random concurrent contralateral biopsies in 108 patients revealed intraductal carcinoma in 6% and invasive carcinoma in 10% of patients (39). Biopsies performed for clinical indications in an additional 22 cases yielded intraductal carcinoma in 5% and invasive carcinoma in 32%. The probability of detecting contralateral invasive carcinoma was significantly greater in women who had multicentric ILC in the ipsilateral breast or who had ipsilateral lymph node metastases.

Several growth patterns may be encountered in lesions classified as classic ILC. The common denominator is the virtual absence of solid, alveolar, papillary, and gland-forming aggregates of cells. In the two-dimensional plane of a histologic section, the slender strands of cells are arranged in a linear fashion, with one or two cells across (Fig. 19.1). If the tumor cells are arranged around ducts and lobules in a concentric fashion, the distribution is described as having a “targetoid” (or “bull’s eye”) appearance (Fig. 19.2). In a minority of cases, the linear strand-forming pattern is not conspicuous, and the tumor cells tend to grow mainly in dispersed, disorderly foci
(Fig. 19.3). The tumor cells in such foci may be small enough to be mistaken for lymphocytes or plasma cells, especially in areas of fibrosis or amid adipose tissue when sections are examined at lower magnification in a frozen section or in a needle core biopsy (NCB) specimen (Figs. 19.4 and 19.5). ILC is only rarely accompanied by a notable lymphocytic reaction (Fig. 19.6), although the term “lymphoepithelioma-like carcinoma” has been applied to an ILC with prominent lymphocytic reaction (40). One such tumor proved to be negative for Epstein-Barr virus.

Occasionally, the sample obtained in a NCB procedure contains minimal, histologically inconspicuous, evidence of ILC that can easily be overlooked after being mistaken for a lymphocytic infiltrate (41) (Figs. 19.7 and 19.8). When LCIS is identified in a NCB specimen, all sections should be vigilantly inspected for foci of occult invasion. A cytokeratin immunostain can be helpful in detecting inconspicuous ILC (Fig. 19.9).

All of the cytologic appearances found in LCIS may also be present in ILC. Classic ILC consists of small, uniform cells with


round nuclei and inconspicuous nucleoli. A variable proportion of cells have intracytoplasmic lumina (Fig. 19.10). Mucin is demonstrable in these vacuoles with the mucicarmine and Alcian blue stains (42,43). When the secretion is prominent, the cells assume a signet ring configuration. The majority of so-called signet ring cell carcinomas, but not all, are forms of ILC (5,42,43,44).