Resident Program - Case of the Month

December 2023 – Presented by Dr. Lorene Chung (Mentored by Dr. Frank Melgoza)

Discussion

Lobular carcinoma in situ (LCIS) originates in the terminal duct lobular units (TDLUs) and is a non-invading neoplastic proliferation of cells that have lost their cohesive abilities. Clinically, LCIS has no specific features as the lesions are usually an incidental microscopic finding in breast biopsies performed for other indications. ¹

Under the microscope, classic LCIS is characterized by monomorphic proliferation of small, dyscohesive cells that have 2 types of nuclei: Type and/or type B. Type A cells have hyperchromatic nuclei that are 1-1.5x the size of a lymphocyte. Type B cells have slightly larger, vesicular nuclei that are 2x the size of a lymphocyte. ² These cells fill and expand >50% of the acini of a TDLU.

Loss of E-cadherin staining is helpful in distinguishing between lobular carcinoma in situ and ductal carcinoma in situ (DCIS). Inactivation of the cadherin-1 (CHD1) gene leads to inactivation or loss of function of E-cadherin, a cell adhesion molecule expressed in normal breast tissue.¹ E-cadherin is a calcium-dependent glycoprotein. During signal transduction, the cytoplasmic tail of E-cadherin associates with alpha-catenin, beta-catenin, gamma-catenin, and p120. Inactivation of CHD1 results in loss of cell-cell adhesion, increased cell proliferation, and altered TDLU architecture. Greater than 95% of LCIS cases lack E-cadherin with a subsequent loss of alpha, beta, and gamma catenin.²

The TriView™ Breast triple stain is a combination of CK5, p63, and CK8/18 and was used in this case to help determine whether this lesion was invasive. CK5 (cytoplasmic) and p63 (nuclear) stains myoepithelial cells brown while CK8/18 labels the cytoplasm of ductal/lobular epithelium red.

References

Foote FW, Stewart FW. "Lobular carcinoma in situ: A rare form of mammary cancer". Am J Pathol. 1941 Jul;17(4):491-496.3. doi: 10.3322/canjclin.32.4.234. PMID: 19970575; PMCID: PMC1965212.

Schnitt SJ, Brogi E, Chen YY, King TA, Lakhani SR. "American Registry of Pathology Expert Opinions: The Spectrum of Lobular Carcinoma in Situ: Diagnostic Features and Clinical Implications". Ann Diagn Pathol. 2020 Apr;45:151481. doi: 10.1016/j.anndiagpath.2020.151481. Epub 2020 Feb 15. PMID: 32120324; PMCID: PMC7401835.

Singhai R, Patil VW, Jaiswal SR, Patil SD, Tayade MB, Patil AV. "E-Cadherin as a diagnostic biomarker in breast cancer". N Am J Med Sci. 2011 May;3(5):227-33. doi: 10.4297/najms.2011.3227. PMID: 22558599; PMCID: PMC3337742.

Rakha, Emad A., FRCPath; Patel, Arjun, B.Sc.; Powe, Des G., Ph.D.; Benhasouna, Ahmed, M.Sc.; Green, Andrew R. PhD; Lambros, Maryou B., Ph.D.; Reis-Filho, Jorge S., FRCPath; Ellis, Ian O., FRCPath. "Clinical and Biological Significance of E-cadherin Protein Expression in Invasive Lobular Carcinoma of the Breast". The American Journal of Surgical Pathology 34(10):p 1472-1479, October 2010. | DOI: 10.1097/PAS.0b013e3181f01916