Cell morphology is the study of the shape, structure, and size of cells. In cancer, it refers to the physical appearance of cancer cells compared to healthy cells. These visual characteristics are important for diagnosis, as they provide the first clues that a cell has become malignant. Examining these features under a microscope is a standard practice in pathology.
Distinguishing Features of Cancer Cells
A primary indicator of cancerous changes is pleomorphism, which is the variation in the size and shape of cancer cells within a tumor. Unlike normal tissues where cells are uniform, cancerous tissues are composed of a disordered collection of cells. This irregularity reflects the genetic instability that drives cancer, leading to a loss of the structural consistency seen in healthy tissues. The difference is like a well-constructed brick wall versus a haphazard pile of stones.
The nucleus of a cancer cell undergoes significant alterations. A prominent change is an increased nuclear-to-cytoplasmic ratio, meaning the nucleus becomes disproportionately large relative to the cell’s cytoplasm. The nuclear membrane often appears irregular, with indentations and folds. When stained, the nucleus also tends to absorb more dye, a characteristic known as hyperchromasia, making it appear darker than a normal cell’s nucleus.
Within the nucleus, structures called nucleoli also show distinct changes. In healthy cells, nucleoli are small and often difficult to see, but in cancer cells, they become larger and more numerous, a condition called macronucleoli. These prominent nucleoli are a sign of increased ribosomal RNA production, which is necessary to support the rapid growth and protein synthesis fueling uncontrolled cell proliferation.
Healthy cells grow in an orderly manner, adhering to one another in well-defined arrangements to form tissues. Cancer cells lose this organization and orientation. They pile up, disregard tissue boundaries, and lack the structured architecture of normal cells. This loss of arrangement is a manifestation of overriding contact inhibition, where normal cells stop dividing when they touch neighboring cells.
Cancer cells are also characterized by increased and abnormal mitotic activity. Because they divide uncontrollably, a higher number of cells undergoing mitosis can be seen in a tissue sample. The division process itself can be flawed, and pathologists identify atypical mitotic figures. These are abnormal structures that form during cell division, like tripolar spindles, resulting in an unequal distribution of chromosomes to daughter cells.
The Role of Morphology in Cancer Diagnosis
The visual identification of cancer cell characteristics is a primary step in diagnosis. The process begins when a physician collects a tissue sample from a suspected tumor in a biopsy. This sample is sent to a pathology laboratory, where it is prepared for microscopic examination. The tissue is preserved, embedded in wax, and sliced into extremely thin sections.
These thin tissue sections are mounted on glass slides and treated with specialized dyes. The most common staining combination, hematoxylin and eosin (H&E), gives cellular structures distinct colors. Hematoxylin stains the cell nucleus blue or purple, while eosin stains the cytoplasm and connective tissue pink. This color contrast allows a pathologist to see the cellular details.
Under the microscope, the pathologist searches for the morphological hallmarks of cancer. They analyze cell size and shape, nuclei, nucleoli, and the overall tissue organization. The presence of features like pleomorphism and a high nuclear-to-cytoplasmic ratio helps distinguish between a benign (non-cancerous) and a malignant (cancerous) tumor. This morphological analysis is a primary method for confirming a cancer diagnosis.
Grading and Staging Cancers
After a diagnosis, pathologists perform cancer grading, a system that classifies cancer cells based on how abnormal their morphology appears. This process, also known as differentiation, assesses how much the cancer cells resemble the normal cells of their original tissue. The grade reflects the tumor’s aggressiveness and is assigned on a numerical scale, such as Grade 1, 2, or 3.
Low-grade cancers (Grade 1) are well-differentiated, meaning the cells look similar to normal cells and are associated with slower growth and a better prognosis. In contrast, high-grade cancers (Grade 3 or 4) are poorly differentiated or undifferentiated, with cells that appear very abnormal and disorganized. These tumors are more aggressive, growing and spreading more quickly.
Grading must be distinguished from staging. While grading is based on cell morphology, staging describes the size of the primary tumor and how far it has spread. Staging is determined through imaging tests, such as CT scans or MRIs, and pathological findings. It provides information about the cancer’s extent, which is used to guide treatment decisions.
Morphological Variations in Different Cancers
The term “cancer” encompasses many diseases, and the morphology of cancer cells can vary significantly depending on the cancer type and its tissue of origin. This variation helps pathologists identify the cancer’s origin, which influences treatment strategies. Different cancer types have characteristic cellular shapes and growth patterns that provide clues about their lineage.
For example, adenocarcinomas are cancers that develop in glandular tissues, which produce substances like mucus or hormones. Under a microscope, adenocarcinoma cells often form gland-like structures or tubules. These formations can appear as circular or irregularly shaped rings of cells, reflecting their glandular origin.
In contrast, squamous cell carcinomas arise from the flat, scale-like cells that make up the surface of the skin and the lining of certain organs. The morphology of these cancer cells often mimics their healthy counterparts. They appear as flattened, irregular-shaped cells that may produce keratin, a protein found in skin cells.
Sarcomas are cancers of connective tissues like bone, muscle, and fat, and present another distinct morphology. These tumors are characterized by spindle-shaped cells, which are elongated and tapered at both ends.