HC9: Nomenclature and grading of cancer

Nomenclature

Mesenchymal tumors:

There are many kinds of mesenchymal tumors:

• Fat: lipo-
• Bone: osteo-
• Fibrous: fibr-
• Cartilage: chondro-
• Blood vessels: hemangio-
• Muscle: leiomyo-/rhabdomyo-

These tumors can be benign of malignant:

• Benign: -oma
  • Cells are nicely organized
• Malignant: -sarcoma
  • Sarcoma means flesh → malignant tumors are fleshy
  • Cells aren’t organized

Epithelial tumors:

Epithelium is the coverage and lining of the body. Tumors can be:

• Glandular or ductal
• Squamous and stratified

Epithelial tumors can be benign of malignant:

• Benign
  • Adenoma
    • Cystadenoma: a cyst originating from a duct
  • Papilloma
• Malignant
  • Carcinoma
    • Adenocarcinoma: carcinoma in the colon
    • Papillary carcinoma

Melanocytes:

Melanocytes can be benign or malignant:

• Benign
  • Nevus: a mole
• Malignant
  • Melanoma
    • In this case, “-oma” stands for a malignant disease

Testicular epithelium:

Tumors in testicular epithelium are always malignant → seminomas.

Totipotent cells can form all kinds of tissues. They are also located in the testis and ovaries. Tumors are called teratomas:

• Benign
  • Mature teratoma
• Malignant
  • Immature teratoma/terato-carcinoma

In women, teratomas are often benign. They can contain all types of tissues, even complete teeth.

Salivary glands:

Salivary glands have many different features. Tumors in salivary glands can vary greatly. They can be benign or malignant:

• Benign
  • Pleiomorphic adenoma
    • Has a high recurrence
  • Many others
• Malignant
  • Mucoepidermoid carcinoma
  • (Basal) adenocarcinoma
  • Acinic cell carcinoma

Grading

Grading defines the impact of grade and stage in different malignancies and can explain the differences between these features. A grade can be used as a biomarker, which is:

• Prognostic: for example of the chances of metastasis
• Predictive: for example of the chances of response to certain types of therapy

For all tumor types, there are different grading systems.

Grading of benign tumors:

There are 4 grades for benign tumors:

• Grade 1: well differentiated → low grade
• Grade 2: moderately differentiated → intermediate grade
• Grade 3: poorly differentiated → high grade
• Grade 4: undifferentiated → high grade

Bloom and Richardson:

Bloom and Richardson made grades which can be used to predict the survival rate, for instance for breast cancer:

• Grade 1 → 75% after 5 years
• Grade 2 → 53% after 5 years
• Grade 3 → 31% after 5 years

Fuhrman grading system:

The Fuhrman grading system can be used in renal cell carcinomas. These cells have clear cytoplasms. The bigger the nucleoli (dots in the nuclei), the higher the grade. There are 4 grades in total.

Gleason scoring system:

The Gleason scoring system can be used in case of prostate cancer. It is based on the amount of nicely formed ducts:

• Grade 1: nearly normal cells
• Grade 2: some abnormal cells, loosely packed
• Grade 3: many abnormal cells
• Grade 4: very few normal cells left
• Grade 5: completely abnormal cells

Disadvantages:

These mentioned grading systems still work, but there are several disadvantages:

• Inter-observer variability
• Tumor biology is more than just growth-patterns + atypia
• More precision is necessary

Markers:

Several markers for the presence of cancer can be stained:

• KI-67: a marker for cell proliferation → more proliferative cells stain darker
  • Only stains cells in the G1-phase
  • If all cells are in the G1-phase, it is a high grade tumor
• P53: important for cell mutation reduction → mutated P53 piles up in a cell → using P53 as a marker can be used for indication of the prognosis
  • Tumors with a p53 mutation have a worse prognosis

Lung cancer has many mutations caused by the damage tobacco does. These mutations can be found and are targetable. Drugs specifically targeted at mutated genes are extremely useful. Nevertheless, in the end tumor cells develop which are resistant to everything.

Immunotherapy

Immunotherapy is one of the most expensive therapies there are. PDL1 is a physiological mechanism. It is used by tumor cells to protect themselves from the immune response. A tumor cell with strong membranous PDL1 expression is invisible for T-cells. Blocking PDL1 with immunotherapy or checkpoint inhibition can be extremely effective → the immune response is no longer useless and attacks the tumor cells. This mechanism plays a role in lung cancer.