A histologic subtype is a specific classification of a disease based on the appearance of cells and tissue when examined under a microscope. Think of it like different varieties of an apple; a Granny Smith and a Red Delicious are both apples, but they have distinct differences. Similarly, two diseases under the same general category, such as lung cancer, can be composed of cells that look and behave very differently.
This classification is based on the microscopic architecture of the cells, including their size, shape, and their relationship to surrounding tissues. Pathologists, doctors who specialize in diagnosing diseases through laboratory analysis, determine the histologic subtype. This detailed identification provides a more precise understanding of a patient’s condition.
Uncovering Histologic Subtypes
The process of identifying a histologic subtype begins with a biopsy, where a small piece of tissue is removed and sent to a pathology laboratory. The sample is treated with chemicals in a process called fixation, which preserves the tissue. It is then embedded in a block of paraffin wax for support, which allows it to be cut into extremely thin slices with a microtome.
These sections are carefully placed on glass slides and treated with stains to make cellular details visible. The most common staining method is Hematoxylin and Eosin (H&E). Hematoxylin colors the cell nucleus a deep blue or purple, while eosin stains the cytoplasm and surrounding connective tissue in shades of pink.
This color contrast allows a pathologist to clearly see the shape of the cells and their organization under a microscope. By observing these patterns, the pathologist identifies the specific histologic subtype. In some cases, more advanced techniques like immunohistochemistry are used, which apply antibodies to detect certain proteins on the cells to further refine the diagnosis.
Histologic Subtypes and Disease Prognosis
Prognosis refers to the expected course and outcome of a disease, and the histologic subtype is a major factor in this forecast. Two cancers in the same organ can have different natural histories based on their microscopic classification. Some subtypes are inherently more aggressive, meaning they tend to grow and spread more quickly than others.
For example, in kidney cancer, studies show that patients with the clear cell histologic subtype generally have a poorer prognosis compared to those with papillary or chromophobe subtypes. A similar principle applies to lung adenocarcinoma, where subtypes with a solid or micropapillary growth pattern are linked to worse outcomes than those with a lepidic pattern.
This prognostic information helps a medical team anticipate the disease’s likely progression. This allows for more informed discussions about the seriousness of the condition and helps establish an appropriate level of monitoring.
Tailoring Treatments with Histologic Subtypes
Identifying the histologic subtype is an important step in developing a personalized treatment strategy. Since different subtypes have unique biological characteristics, they respond differently to therapies like surgery, radiation, and medications. A treatment effective for one subtype may be ineffective for another.
In non-small cell lung cancer (NSCLC), the distinction between squamous and non-squamous subtypes directly influences chemotherapy choices. The drug pemetrexed is a standard treatment for non-squamous NSCLC, such as adenocarcinoma, but it is not recommended for squamous cell carcinoma. This is because the enzyme that pemetrexed targets is present at much lower levels in adenocarcinoma cells.
The subtype also dictates the use of targeted therapies, which are drugs designed to attack cancer cells with specific molecular changes. For instance, certain lung adenocarcinomas have mutations in a gene called EGFR, and patients with these tumors can be treated with drugs that specifically block the EGFR protein. Histology also provides clues about the tumor’s microenvironment, which can predict whether a patient will benefit from immunotherapies that activate the body’s immune system.
Illustrative Histologic Subtypes in Practice
Looking at specific diseases highlights the importance of subtyping. In lung cancer, two common subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma. Adenocarcinoma develops in the outer regions of the lungs and is characterized by cells that can form gland-like structures. In contrast, squamous cell carcinoma usually starts in the central airways and is composed of flatter cells. This distinction impacts prognosis, as patients with stage I adenocarcinoma may have a better survival rate than those with stage I squamous cell carcinoma.
Another example is found in breast cancer, with the two most frequent subtypes being invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). IDC, which accounts for most cases, consists of cancer cells that form a cohesive mass. ILC is characterized by smaller cells that infiltrate the tissue in single-file lines, a pattern caused by the loss of a cell-adhesion protein called E-cadherin.
This infiltrative growth can make ILC more difficult to see on mammograms and may lead to different surgical approaches. While both are often driven by hormones, their distinct biology can influence long-term recurrence patterns and response to specific therapies.