Invasive Cribriform Carcinoma
FREDERICK C. KOERNER
Cribriform carcinoma is a well-differentiated variant of invasive duct carcinoma. Many of these tumors are probably classified as low-grade invasive duct carcinomas without acknowledging the cribriform growth pattern. Because the information thus far available is limited, it has not been possible to determine whether invasive cribriform carcinoma represents a low-grade variant of invasive duct carcinoma or a specific subtype of carcinoma. For the present, it seems appropriate to employ a diagnosis of “invasive duct carcinoma, cribriform type” to identify these lesions for further study. Those tumors in which the majority of the invasive carcinoma exhibits a cribriform pattern are termed “classical invasive cribriform carcinomas.” Some of these tumors have cribriform and tubular components. Tumors in which less than 50% of the lesion has an invasive cribriform pattern and in which the majority displays neither cribriform nor tubular patterns are designated “mixed invasive cribriform carcinoma.”
Three major studies of invasive cribriform carcinoma have been published. Among 1,003 invasive breast carcinomas treated at the University of Edinburgh in a 10-year period, Page et al.1 found 35 classical (4%) and 16 mixed (2%) invasive cribriform carcinomas. Venable et al.2 reviewed 1,087 primary breast carcinomas at the George Washington University and reported that 32 (3%) were pure or largely invasive cribriform carcinomas and that 30 (3%) were mixed invasive cribriform carcinomas. Marzullo et al.3 found three pure and two mixed cases in a series of 1,759 infiltrating carcinomas, representing 0.3% of the entire group.
The ages of the female patients ranged from 7 to 91 years. Page et al.1 found that women with classical invasive cribriform carcinoma tended to be younger and to have smaller tumors than women with mixed lesions. Marzullo et al.3 described three women with pure tumors who were between the ages of 70 and 90 years. Two reported patients were men.2,4 Choi et al.5 described a 6-cm invasive cribriform carcinoma occupying a 10-cm malignant phyllodes tumor (PT) in a 62-year-old woman. In a study of eight cases, mammograms revealed spiculated masses measuring 20 to 35 mm in four patients.6 Two of these lesions contained a few punctate calcifications, and so did the case described by Nishimura et al.4 Invasive cribriform carcinomas do not have consistent sonographic finding.4,6,7 Magnetic resonance imaging (MRI) performed on one tumor displayed homogeneous early enhancement with a delayed wash-out kinetic pattern compatible with a carcinoma.7
No specific gross pathologic features have been noted. Data from two studies suggested that a small but distinct proportion of invasive cribriform carcinomas occur as multifocal masses.1,3 In one study, 7 of 35 (20%) patients with classical and 1 of 16 (6%) patients with mixed invasive cribriform carcinoma had macroscopically evident multifocal invasive foci in the affected breast.1 One patient studied by Marzullo et al.3 had two masses spanning 1.6 and 0.4 cm in the same breast.
The invasive component of cribriform carcinoma exhibits the same sieve-like growth pattern that characterizes conventional cribriform ductal carcinoma in situ (DCIS) (Fig. 26.1). The rounded and angular masses of uniform, well-differentiated tumor cells are embedded in variable amounts of collagenous stroma. Sharply outlined, round, or oval glandular spaces are distributed throughout these tumor aggregates, creating a fenestrated appearance. Mucin-positive secretion is present in varying amounts within the lumens,8 which may also contain microcalcifications.9 Specimens obtained by needle aspiration demonstrate bland ductal cells arranged in monolayered sheets or in cohesive three-dimensional clumps. Myoepithelial cells and naked nuclei do not appear obvious.10 The tumor cells do not contain argyrophilic granules when examined with the Grimelius stain,1 and myoepithelial cells are not demonstrable by actin immunostaining. The in situ component has a cribriform pattern in most but not all classical invasive cribriform carcinomas. Perineural invasion is rarely found in this type of low-grade carcinoma (Fig. 26.2