Cancer Pathology Lecture - Dr. D. Owen

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Introduction

At the outset is important to realize that cancer is not a single disease. For example, cancer of the breast is quite different from cancer of the ovary: it has different causes, different methods of spread and quite different methods of treatment. Furthermore, even arising within a single organ there are different pathologic types of cancer and the correct identification and diagnosis of these types is in most instances essential before effective treatment can commence.

The role of the pathologist in the management of cancer is twofold. First a biopsy (a small piece) of a suspected cancer is taken and submitted to the laboratory for (a) confirmation that cancer is in fact present and (b) determination of type. Cancers are classified and treated according to histologic type. Oncologists know from their experience which types of treatment are likely to be effective in different types of cancer. In some cancers more radical surgical treatment is performed and the resulting excised tissue is sent to the laboratory. The second role of the pathologist is then to assess the completeness of surgical excision and to determine whether additional treatment (e.g. radiotherapy or chemotherapy) is required. In modern oncologic practice cancer treatment cannot proceed until the diagnosis is confirmed histologically. This is because benign mimics of cancer exist and the most reliable way of diagnosis is by histologic examination. To omit this step is to risk overtreating a patient for a benign condition.

Some definitions are now necessary. It is essential for students to understand some technical jargon, which here is kept to a minimum:

Tumor: Strictly speaking this means a swelling of any sort. However, modern usage has equated the term with a neoplastic mass.

Neoplasm: An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change. Neoplasms may be benign or malignant.

Cancer: A generic term for all malignant neoplasms.

Hyperplasia: An increase in the number of cells in an organ or tissue in response to a stimulus. When the stimulus is removed the hyperplasia regresses.

Hypertrophy: An increase in the size of cells within an organ in response to a stimulus. When the stimulus is removed the cells return to normal size.

Atrophy: A reduction in either the size of cells or number of cells within a tissue. This can be reversible when it represents part of a response to an external stimulus or it can be part of the normal aging process.

Dysplasia: A premalignant change in cells (usually epithelium) characterized by disorderly growth and morphologic changes in cell nuclei.

Classification of Neoplasia

The most basic subdivision is into benign and malignant tumors. Benign tumors grow slowly and their growth remains localized. They may press on adjacent organs but do not invade, destroy or metastasize. Simple excision is usually curative. Rarely, they prove fatal if they occur in a surgically inaccessible site of the body. Malignant tumors grow rapidly: they directly invade and destroy adjacent organs. In addition, they have the power to metastasize i.e. spread to other parts of the body usually via the blood stream, the lymphatic system or across serous membranes (peritoneum, pleura, pericardium).

Malignant tumors present with an organ of the body may be primary or metastatic. It is always worthwhile to consider the possibility that a neoplasm is metastatic, particularly if it is located in the lung, liver, brain or bones. In general, secondary tumors carry the same biologic characteristics and response to treatment as the primary tumor from which they arose.

The principle of the histologic classification of neoplasia is therefore firstly to identify which organ (or tissue) they arose from and secondly to determine the histologic type. In general, neoplasms both benign and malignant, histologically resemble the tissue from which they arose. Within the body the major tissues are as follows: (a) epithelium (includes skin, the lining of the gastrointestinal and urinary tracts and solid abdominal organs e.g. liver, kidney and pancreas); (b) connective tissue (includes muscle, fat, bone, cartilage, nerves and blood vessels); (c) lymphoid and blood forming tissues (includes lymph node, spleen, bone marrow and thymus); (d) central nervous system (includes neurons and glia) and; (e) germ cells (includes testis and ovary). Malignant epithelial tumors are called carcinomas and malignant connective tissue tumors are called sarcomas. The benign equivalents of these tumors have various names, which sometimes appear to have been given in an illogical fashion.

Nomenclature of Epithelial Tumors
Type of Epithelium Squamous Glandular Transitional Liver Gastrointestinal endocrine cells	Benign Squamous papilloma Adenoma Transitional papilloma Adenoma	Malignant Squamous Carcinoma Adenocarcinoma Transitional Carcinoma Hepatocellular Carcinoma Carcinoid/small cell carcinoma

Nomenclature of Connective Tissue Tumors
Type of Tissue Bone Cartilage Fat Smooth muscle Voluntary muscle Blood vessel	Benign Osteoma Chondroma Lipoma Leiomyoma Rhabdomyoma Angioma	Malignant Osteosarcoma Chondrosarcoma Liposarcoma Leiomyosarcoma Rhabdomyosarcoma Angiosarcoma

Nomenclature of Blood and Lymphoid Tumors
Type of Tissue Lymphocytes Marrow granulocytes Marrow lymphocytes Plasma cells	Benign  -  -  -  -	Malignant Lymphoma Myeloid leukemia Lymphocytic leukemia Myeloma

These lists are incomplete and many other special types of neoplasm exist. These should be learned when you study the various organ systems. Since the emphasis for this oncology section of the course is breast tumors more details of the classification of breast tumors is provided.

Breast Neoplasia

The breast is a complex organ which contains epithelial tissues and connective tissues including fat, fibrous tissue and vessels. Epithelial tissues are of two types: the lobules and the ducts. In non-pregnant women the lobules are in a resting phase but during pregnancy and lactation they expand and secrete milk. The ducts convey the milk to the nipple. Near the lobules the ducts are small caliber. Near the nipple the ducts become fewer but larger. Specialized loose fibrous connective tissue is present within the lobules that accommodates physiologic expansion of the breast during pregnancy. Denser fibrous connective tissue is present in extralobular sites to provide structural support.

The vast majority of breast neoplasms are epithelial in origin: either ductal or lobular. When carcinoma develops it starts initially within the duct or lobule and only later in the course of the disease does it break through the basement membrane and invade into the fat and connective tissues. During this initial phase it may be referred to as carcinoma-in-situ or more specifically as intraductal or intralobular carcinoma. In the later stages the carcinoma becomes infiltrating ductal or infiltrating lobular carcinoma. For the purposes of management it is essential to separate intraductal (or intralobular) types from infiltrating forms. Infiltrating cancer may have metastasized at the time of diagnosis and may involve axillary lymph nodes. In contrast, carcinoma-in-situ is by definition confined to the breast and is amenable to local surgical excision.

Histologic features used to define the presence of infiltrating carcinoma in breast biopsies include the presence of venous and/or lymphatic invasion.

Grade and Stage

Grade refers to the degree of differentiation of a neoplasm. Grade I (or well differentiated) neoplasms closely resemble the normal tissues from which they are derived. Grade III (or poorly differentiated) only slightly resemble the tissues they are derived from. Patients with Grade III tumors have a poorer prognosis than those with Grade I tumors.

Stage of a tumor refers to the extent of spread. The system used is the TNM (tumor, node, metastasis) system developed by the International Union against Cancer (UICC). The system for breast is as follows:

Tis - Carcinoma-in-situ
T1 - Gross size of tumor is less than 2.0 cm diameter
T2 - Gross size of tumor is between 2-5 cm diameter
T3 - Gross size of tumor is above 5 cm diameter
T4 - Tumor of any size involving chest wall or skin

N0 - No axillary node involved
N1 - Metastases to axillary nodes that are freely mobile
N2 - Metastases to fixed (immobile) axillary nodes
N3 - Metastases to internal mammary nodes

M0 - No metastases outside of local nodes
M1 - Metastases present

Use of these two systems can predict prognosis for an individual patient and also allows comparison of treatment results from one centre to another.