Case of the Month: Breast Pathology

May 2017 Case of the Month authored by Breast Pathologist Jaya "Ruth" Asirvatham, M.D.

History

A 53-year-old female underwent a core biopsy for increasing microcalcifications on mammogram. The core biopsy showed flat epithelial atypia with focal atypical ductal hyperplasia, and the patient subsequently underwent an excisional biopsy. The excision biopsy showed columnar cell hyperplasia, flat epithelial atypia and a focal proliferation of bland glandular structures.

Images related to the case


Figure 1: Proliferation of small glandular structures

Figure 2: High-power view of glands, demonstrating angulated contours and apical snouts

Figure 3: P63 immunostain is negative around these glands, but stains normal myoepithelial cells around benign lobules.

Figure 4: Smooth muscle myosin heavy chain (SMMHC) is negative around these glands, but stains normal myoepithelial cells around benign lobules.

Figure 5: The cells forming the glands are negative for S100. S100 stains occasional myoepithelial cells within normal lobules.

Figure 6: Collagen IV is negative around the glands, but highlights the basement membrane of adjacent structures.

Figure 7: Estrogen receptor uniformly stains the nuclei of the proliferating cells.

 



Diagnosis

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Discussion

Studies have shown that invasive tubular carcinoma is frequently clonally related to flat epithelial atypia and low-grade ductal carcinoma in-situ1. Tubular carcinoma often coexists with columnar cell lesions and lobular carcinoma in-situ, forming a histologic triad known as the Rosen Triad2. The presence of columnar cell changes, flat epithelial atypia or lobular neoplasia should prompt the reviewing pathologist to carefully examine the tissue for tubular carcinoma.

Classical features for tubular carcinoma include small glandular structures, usually composed of cells with bland nuclei. Some glands have angulated contours and the cells forming the glands usually have apical snouts. The key differential diagnoses include:

  • Sclerosing adenosis;
  • Microglandular adenosis; and
  • Tubular adenosis.

Rarely, adenomyoepithelioma may present with a microglandular adenosis pattern.

Myoepithelial stains p63 and smooth muscle myosin heavy chain are useful to demonstrate the myoepithelial cells around sclerosing adenosis, tubular adenosis and adenomyoepithelioma. Microglandular adenosis (MGA) is a benign entity that lacks myoepithelial cells and can be misdiagnosed as invasive tubular carcinoma. The glands are usually small and round, with no angulations or apical snouts, and may contain eosinophilic secretions. Collagen IV or laminin stains are also helpful to demonstrate the presence of basement membrane around the glands in MGA and the lack of basement membrane around tubular carcinoma.

References

  1. Brandt SM, Youn GQ, HOda SA. The “Rosen Triad”: tubular carcinoma, lobular carcinoma in-situ, and columnar cell lesions. Adv Anat Pathol. 2008; 15(3):140-6.
  2. Aulmann S, Elsawaf Z, Penzel R et al. Invasive tubular carcinoma of the breast frequently is clonally related to flat epithelial atypia and low-grade ductal carcinoma in-situ. Am J Surg Pathol. 2009; 33 (11):1646-53.
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