In pathology, the term anaplastic describes cells that have lost their normal structure and specialized function. Viewed under a microscope, these cells appear to have reverted to a more primitive, undifferentiated state, departing from the mature cells of their original tissue. The term itself, with roots in Greek, suggests a process of forming backward.
The presence of anaplasia means the cells no longer perform their usual roles and have lost the distinct features that define their tissue type. This loss of differentiation is a primary characteristic of anaplastic cells.
Cellular Characteristics of Anaplasia
When a pathologist examines tissue with anaplastic cells, they observe distinct microscopic features. A prominent feature is pleomorphism, a wide variation in cell size and shape. Unlike uniform healthy tissue, anaplastic tissue contains a chaotic mix of cells, with some much larger than normal and others smaller and oddly shaped.
Another feature is abnormal nuclear morphology. The nucleus becomes disproportionately large, sometimes approaching the size of the cell itself and altering the normal nuclear-to-cytoplasmic ratio from 1:4 to as high as 1:1. These nuclei are often irregularly shaped and stain darkly (hyperchromatism), reflecting an increased amount of DNA.
An increase in mitosis (cell division) is also identified. In anaplastic tissue, cell division is frequent, chaotic, and abnormal. Instead of orderly bipolar spindles, bizarre multipolar mitotic figures are observed, indicating uncontrolled proliferation.
Anaplastic cells also exhibit a loss of polarity. In healthy tissues, cells are organized and oriented in a specific way. Anaplastic cells lose this structure, growing in disordered sheets without any recognizable pattern or architectural arrangement.
The Role of Anaplasia in Tumor Grading
Tumor grading is a system pathologists use to classify a tumor based on how abnormal its cells and tissue appear microscopically. This classification helps predict a tumor’s potential to grow and spread. The presence and degree of anaplasia are primary factors in assigning a tumor’s grade.
Tumor grades are often assigned on a scale, such as from Grade 1 (well-differentiated) to Grade 4 (poorly differentiated). Grade 1 tumors resemble normal tissue and are slow-growing. In contrast, tumors with a high degree of anaplasia are classified as poorly differentiated or undifferentiated and receive a high grade, like Grade 3 or 4. This high-grade designation signifies a more aggressive tumor with rapid, uncontrolled growth.
While a general grading system is common, some cancer types have specific classification schemes. For example, prostate cancer uses the Gleason score, and breast cancer often uses the Nottingham histologic score. These specialized systems still rely on the underlying principles of assessing differentiation and cellular abnormality.
Types of Anaplastic Cancers
The term “anaplastic” is part of the diagnosis for several distinct types of aggressive cancers. These tumors are characterized by their lack of differentiation, meaning the cancer cells have lost the features of the normal cells from which they developed.
Anaplastic Thyroid Cancer
Anaplastic thyroid cancer is a rare but highly aggressive form, accounting for 1-2% of all thyroid malignancies. This cancer is known for its rapid growth, often presenting as a quickly enlarging neck mass that can cause breathing and swallowing difficulties. It predominantly affects individuals over age 60 and is more common in women.
Anaplastic Astrocytoma
Anaplastic astrocytoma is a malignant brain tumor that develops from star-shaped glial cells called astrocytes. According to the World Health Organization (WHO) classification, it is a grade III tumor, indicating a high-grade malignancy. Symptoms depend on the tumor’s location in the brain but can include headaches, seizures, and changes in behavior or cognitive function.
Anaplastic Large-Cell Lymphoma (ALCL)
Anaplastic large-cell lymphoma (ALCL) is a rare type of non-Hodgkin lymphoma, a cancer of the lymphatic system. The name reflects the appearance of the cancer cells, which are abnormally large T-cells. ALCL is characterized by the presence of a marker called CD30 on the surface of the cancer cells. The disease can be systemic, affecting lymph nodes and other organs, or cutaneous, limited to the skin. Systemic ALCL is further divided into ALK-positive and ALK-negative types, depending on the presence of a protein that influences prognosis and treatment.
Diagnostic Process and Prognosis
Diagnosing an anaplastic tumor begins with a biopsy, where a small tissue sample is sent to a pathologist for microscopic examination. A fine-needle aspiration is often a first step, especially for thyroid nodules. If results are inconclusive, a core needle biopsy may be performed to obtain a more substantial tissue sample.
After analysis, the pathologist confirms the presence of anaplastic cells. To determine the extent of the cancer’s spread, imaging studies like CT scans, MRIs, and PET scans are ordered. These tests help show if the tumor has invaded nearby tissues or metastasized to distant organs.
The presence of anaplasia points to a more challenging prognosis. Because anaplastic cells are undifferentiated and multiply rapidly, they are more likely to invade surrounding tissues and metastasize (spread). For instance, anaplastic thyroid cancer often spreads to lymph nodes in the neck and distant sites, and all cases are automatically classified as stage IV due to their aggressive nature. While the prognosis is often poor, factors like the patient’s age, tumor size, and the extent of metastasis can influence the outcome.
Therapeutic Approaches for Anaplastic Tumors
Due to their aggressive nature, anaplastic tumors require intensive, multi-modal treatment plans. The combination of therapies is tailored to the individual based on cancer type, location, and spread. The goal is to control tumor growth, manage symptoms, and improve quality of life.
Surgery is a primary treatment when the tumor is localized and can be safely removed. A surgeon may attempt to remove as much of the tumor as possible in a procedure known as debulking. However, complete removal is not always possible because these tumors often invade surrounding structures.
Radiation therapy uses high-energy rays to destroy cancer cells and shrink tumors. It is often used after surgery to target any remaining cancer cells. Radiation can also be a primary treatment to control tumor growth and alleviate symptoms when surgery is not an option.
Chemotherapy uses drugs to kill rapidly dividing cells throughout the body. This systemic approach is used for cancer that has spread or is at high risk of spreading. The drugs used depend on the cancer type; for example, a combination known as CHOP is a standard treatment for anaplastic large-cell lymphoma.
Newer modalities offer more precise ways to combat these cancers. Targeted therapy uses drugs designed to attack specific genetic mutations in cancer cells, such as BRAF mutations in some anaplastic thyroid cancers. Immunotherapy, on the other hand, works by enhancing the body’s own immune system to recognize and destroy cancer cells. Combining these therapies can improve survival for certain patients.