Case of the Month

Answer:

C.  Lobular carcinoma in situ with comedo necrosis

Discussion

Classic lobular carcinoma in situ is diagnosed when more than half of the acini of a lobular unit are distended and distorted by solid proliferation of loosely cohesive cells with small, uniform nuclei.

Several variants of LCIS have been recognized with increasing frequency because of the presence of microcalcifications detected on screening mammography. These variants demonstrate classic histopathological features of LCIS (loosely cohesive or dyshesive cells growing in a solid growth pattern; patetoid involvement of ducts), but also exhibit other unusual histopathological features like:

1. LCIS with Comedo Necrosis:  Lesions are composed of classical lobular neoplastic cells,  but in addition, contain central areas of comedonecrosis. Calcifications are often associated with the areas of necrosis.
2. Pleomorphic LCIS: Lesions that show marked nuclear pleomorphism with at least a two to threefold variation in nuclear size, nuclear membrane irregularity, and variably prominent nucleoli. Occasionally, the cell may show apocrine features. Comedo necrosis may be seen.

All these variants typically lack E-cadherin expression and display genomic alterations typical of lobular lesions (16q losses and 1q gains).

Differential Diagnosis:

LCIS with Comedo Necrosis versus Ductal carcinoma in situ (DCIS) of low nuclear grade: Low-grade DCIS is composed of small, monomorphic cells, growing in arcades, micropapollae, cribriform or solid patterns. The solid pattern may show microacini in which cells are polarized around small extra-cellular lumina in a rosette-type arrangement.

The presence of a dyshesive growth pattern and prominent intracytoplasmic vacuoles favors a diagnosis of LCIS.  The immunostains for E-cadherin can be helpful in problematic cases.

Pleomorphic LCIS versus high-grade DCIS: The distinction may be difficult, particular when there is central necrosis and calcifications. Features that favor a diagnosis of pleomorphic LCIS are dyshesive appearance, intracytoplasmic vacuoles and the presence classic LCIS in adjacent lobules. The lack of E-cadherin immunohistochemical staining  is helpful in making the diagnosis of pleomorphic LCIS.

 The cells of ductal carcinoma in situ, regardless of architectural pattern or nuclear grade, generally show uniform cell membrane staining for E-cadherin.

Management of LCIS with comedo necrosis: It is considered as a rare variant of lobular carcinoma in situ and few reports have suggested this lesion has more aggressive behavior, with a higher risk of invasion. In general, excision is recommended when this lesion is seen in a core biopsy or when identified at the margin of a lumpectomy specimen. Evaluation of 3 additional levels of the block to ascertain absence of concurrent invasive carcinoma is also advised.

References:

1. Sunil R. Lakhani, Ian O. Ellis, Stuart J. Schnitt, et. al. WHO Classification of Tumors of the Breast. 4th ed. WHO Press, 2012: 1-94.
2. Fadare, O et al. Lobular intraepithelial neoplasia [lobular carcinoma in situ] with comedo-type necrosis: A clinicopathologic study of 18 cases. Am J Surg Pathol. 2006 Nov;30(11):1445-53.
3. California Tumor Tissue Registry, 139th Semi-Annual Pathology Cancer Seminar. 2015 Dec: 1-15.

Figures:

Figure 1 - Click to enlarge
MRI of right breast shows non-mass enhancement (see arrow).

Figure 2 - Click to Enlarge
Low –power view shows ducts that contain A. Solid proliferation of dyshesive cells. B. An area of comedo necrosis and calcifications. C. Dyshesive cells with intracytoplasmic vacuoles.

Figure 3 - Click to Enlarge
E-cadherin immunostain shows no immunoreactivity in tumor cells.  However, the E-cadherin staining is present in the surrounding mypepithelial cells.