Oncopathology

·         It is important to understand the difference between the grading and staging of a tumor. First of all, these terms are applied to malignant neoplasms and not to benign neoplasms. Basically, grading is done histologically, while staging is done clinically.

Grading of a malignant tumor is based on the histologic degree of differentiation of the tumor cells and on the number of mitoses that are present. These histologic features are thought to be indicators of the aggressiveness of the malignant neoplasm.

In contrast to grading, the staging of cancers is based on the size of the primary lesion, the presence of lymph node metastases, and the presence of bloodborne metastases. These characteristics are determined by clinical means.

Staging has proved to be of greater clinical value than grading.

·         beta-naphthylamine is an exception to the general rule involving cytochrome P450, as the hydrolysis of the nontoxic conjugate occurs in the urinary bladder by the urinary enzyme glucuronidase.

·         PTHrP: bronchogenic Ca, clear cell carcinomas of the kidney,endometrial adenocarcinomas, and transitional carcinomas of the urinary bladder.

·         Hairy cells stain for acid phosphatase, and the reaction is refractory to treatment with tartaric acid [tartrate-resistant acid phosphatase (TRAP)]. These hairy cells also express pan–B cell markers (CD19 and CD20), the monocyte marker CD11c, and the plasma cell marker PCA-1.

·         IMPORTANT CANCER GENES:

Growth Factors

1. c-sis

• β chain of platelet-derived growth factor

• astrocytomas and osteogenic sarcomas

Growth Factor Receptors

1. c-erb B1

• receptor for epidermal growth factor

• breast cancer and squamous cell carcinoma of the lung

2. c-neu

• receptor for epidermal growth factor

• breast cancer

3. c-fms

• receptor for colony-stimulating factor (CSF)

• leukemia

Abnormal Membrane Protein Kinase

1. c-abl

• membrane tyrosine kinase

• chronic myelocytic leukemia (CML)

GTP-Binding Proteins

1. c-ras

• product is p21 (protein)

• adenocarcinomas

Nuclear Regulatory Proteins

1. c-myc → Burkitt’s lymphoma

2. N-myc → neuroblastoma

3. L-myc → small cell carcinoma of the lung

4. c-jun

5. c-fos

Point Mutations

• c-ras → adenocarcinomas

Translocations

• c-abl on chromosome 9 → CML

• c-myc on chromosome 8 → Burkitt’s lymphoma

• bcl-2 on chromosome 18 → nodular lymphoma

Gene Amplification

• N-myc → neuroblastoma

• c-neu → breast cancer

• c-erb B2 → breast cancer

Tumor Suppressor Genes

• Rb → retinoblastoma and osteogenic sarcoma

• p53 → many tumors and the Li-Fraumeni syndrome

• WT1 → Wilms’ tumor and aniridia

• NF1 → neurofibromatosis type 1

·         Malignant carcinomas of the breast may be either noninvasive or invasive.

Noninvasive carcinomas (carcinoma in situ) may be located within the ducts (intraductal carcinoma) or within the lobules (lobular carcinoma in situ). There are several variants of intraductal carcinoma, including comedocarcinoma, cribriform carcinoma, and intraductal papillary carcinoma. Comedocarcinoma grows as a solid intraductal sheet of cells with a central area of necrosis. It is frequently associated with the erb B2/neu oncogene and a poor prognosis. Cribriform carcinoma is characterized by round, ductlike structures within the solid intraductal sheet of epithelial cells, while intraductal papillary carcinoma has a predominant papillary pattern.

In contrast, invasive malignancies are characterized by infiltration of the stroma, which may produce a desmoplastic response within the stroma (scirrhous carcinoma). Infiltrating ductal carcinomas also produce yellow-white chalky streaks that result from the deposition of elastic tissue around ducts (elastosis). Other patterns of invasion that produce specific results include infiltration of cells in a single file in infiltrating lobular carcinoma and mucin production in colloid carcinoma.