A 62-year-old woman comes to the office after finding a lump in her breast. Physical examination shows a firm, immovable, irregularly shaped mass. Mammography is performed and reveals a spiculated, calcified lesion not seen on prior studies. Tissue biopsy shows invasive ductal carcinoma composed of anaplastic cells. Which of the following microscopy descriptions most likely represents a tumor of similar histologic grade?
Tumors described as well differentiated (ie, low grade) contain neoplastic cells that are similar in appearance and function to normal cells in the tissue of origin. In contrast, tumors described as poorly differentiated (ie, high grade) contain neoplastic cells that lack most of the characteristic features of the cells in the original tissue. Neoplastic cells that exhibit a complete lack of differentiation to the cells in the tissue of origin are termed anaplastic, as they are in this patient's biopsy findings.
Anaplastic tumors typically demonstrate the following features:
Loss of cell polarity with complete disruption of normal tissue architecture (eg, cells coalesce into sheets in a disorganized, infiltrative manner)
Significant variation in the shape and size of cells (ie, cellular pleomorphism) and nuclei (ie, nuclear pleomorphism), including formation of giant tumor cells (which may be multinucleated)
Disproportionately large nuclei (ie, high nucleus/cytoplasm ratio) that are often deep staining (ie, hyperchromatic) with coarsely clumped chromatin and large nucleoli
Numerous, often abnormal, mitotic figures
(Choice A) Bronchial epithelial cells can produce keratin after undergoing a phenotypic substitution from columnar to squamous epithelium (ie, metaplasia), which often occurs in response to irritants (eg, tobacco smoke). Although metaplasia is reversible, long-term irritant exposure can lead to malignant transformation; squamous cell carcinoma is frequently preceded by squamous metaplasia within the bronchi.
(Choices B, C, and D) Cells in these 3 tumors are performing functions that are normally performed by cells in the tissue of origin: colon epithelial cells forming glands, hepatocytes synthesizing bile, and keratinocytes producing keratin. As a result, these tumor cells would likely be characterized as well differentiated, not anaplastic.
Educational objective:
Undifferentiated (ie, anaplastic) tumors bear no resemblance to the tissue of origin. They are composed of pleomorphic cells with large, hyperchromatic nuclei that grow in a disorganized manner. Anaplastic tumors frequently contain numerous abnormal mitotic figures and giant cells.