Thursday, October 2, 2008

Neoplasms: Excerpts 3

Neoplasms: principles of development and diversity was published last week. In the next few blogs, I will provide some short excerpts from the book.


In metastasis, tumor cells leave the primary tumor site and travel to some anatomically distant (or at least noncontiguous) location, where they form a growing mass. There are many steps involved in metastasis, and it is no wonder that metastasis is a late event in carcinogenesis that follows the acquisition of invasiveness.

Steps in Metatastasis

1. A tumor cell must invade through the wall of a lymph vessel or a blood vessel.

2. Once inside the vessel, the tumor cell must be carried away from the primary tumor to another site, still within the vessel, where it may reside for some indeterminate time.

3. The tumor cells residing inside the lymphatic vessel must invade through the vascular endothelium into the surrounding tissue.

4. The invading cell or cells must begin to grow.

5. The growing colony must adjust to its new microenvironment and must eventually attract the growth of vessels from which it can derive oxygen and other external nutrients.

Each of the steps of metastasis provides opportunities for a fledgling clone of tumor cells to die, and each step may take time (days, months, or years) while the clone acquires the biological prerequisites for the next step. The time between the seeding of a tumor cell into the lymphatic circulation (the small vessels that lead to lymph nodes), and the clinical observation of a metastatic growth, is called dormancy. Dormancy is discussed in depth in Chapter 2. The time between tumor seeding and the appearance of a metastatic lesion can depend on a great many factors. If the seeded tumor cells have all of the properties necessary to complete the steps of metastasis, then a metastasis may become clinically apparent soon after the primary tumor has begun to invade. For example, if cells were seeded by a metastatic lesion (not from the primary tumor), then the second generation metastatic cells might arrive at their metastatic site pre-equipped for successful growth. In this case, metastases might occur quickly. Alternately, host factors (properties of the non-tumorous cells of the organism) may provide barriers to tumor metastasis. For example, tumor cells that have seeded into the lymphatics might be filtered, trapped, and destroyed in lymph nodes through an immunologic reaction.

Given the complexity of metastasis, you might think that only malignant cells could manage the task. Surprisingly, metastasis is also seen in normal tissues. All blood cells move through the circulation through a process indistinguishable from metastasis. White bloods cells (leukocytes), in response to inflammatory chemokines, will attach to a vessel wall, move through the wall, and proceed to invade local tissues until they arrive at the site of inflammation (the site of highest chemokine concentration). Leukocytes are all highly invasive and metastatic. The only feature that distinguishes normal leukocytes from cancer cells is their controlled growth. The growth of the leukocyte population in response to an infectious process is self-limited. Growth stops when the infection ceases. The most significant clinical property that distinguishes physiological neutrophilia (increase in neutrophils, the most common type of leukocyte) from chronic myelogenous leukemia (the neoplasm caused by an increase in neutrophils) is growth persistence. Chronic myelogenous leukemia gets worse and worse over time. Physiologic neutrophilia eventually plateaus or returns to normal levels.

In Chapter 9, we examine some nonmalignant proliferative disorders of myeloid and lymphoid cells, all of which have clinical features that closely resemble leukemias and lymphomas.

In chinchillas, the normal placenta both invades and metastasizes (5). Trophoblastic tissue invades into uterine vessels, passes into the general circulation, and seeds the lungs. It is normal for a chinchilla mother to harbor pulmonary placental nodules that persist for up to 2 months after delivery. In humans, trophoblastic invasion of the myometrium must be well controlled. Otherwise, harm can come to fetus and mother. Placenta accreta occurs when the placenta attaches directly to the myometrium with deficient development of decidual (maternally-derived) cells between the invading trophoblasts and the myometrium. If the placenta invades deeply into the myometrium, this is called placenta increta. If the placenta invades through the myometrium, this is called placenta percreta. All three conditions are associated with medical risks to baby and mother. We discuss human gestational trophoblastic disease in Chapter 20.

(to be continued)

Chapter 1 Table of Contents:

1 What Properties Are Shared by All Cancers? 3

1.1 Background 3

1.2 Are There Any Properties of Neoplasms that Are Not Found in Normal Cells? 4

1.3 Persistent Growth in Normal Cells 4

1.4 Invasion by Normal Cells 5

1.5 Metastasis by Normal Cells 5

1.6 Is There a Common Temporal Sequence Leading to the Development of Cancer? 7

1.7 Why Is It Important to Treat Cancers Early? 7

1.8 Cancer Morphology 8

1.9 General Rules for Naming Neoplasms 8

1.10 What Is a Cytologic Diagnosis? 9

1.11 Morphology of Malignant Cells 10

1.12 Cancerous Atypia and Reactive Atypia 12

1.13 How Can You Distinguish Reactive Atypia from Cancerous Atypia? 13

1.14 Dysplastic Cells and How They Differ from Cancer Cells 14

1.15 Nuclear Atypia in Cancer Cells 15

1.16 Why Are the Nuclei of Malignant Cells Different from Nuclei of Normal Cells? 15

1.17 Tumor Monoclonality 15

1.18 Monoclonal Proliferative Lesions 16

1.19 Clonal Expansion in Paroxysmal Nocturnal Hemoglobinuria 17

1.20 Clonal Expansions of Normal Cells that May Not Lead to Cancer 18

1.21 Polyclonal Expansions that May Lead to Monoclonal Cancer 18

1.22 Tumor Growth Regulation and Tumor Autonomy 18

1.23 Limits on Tumor Autonomy 19

Summary 19

The full table of contents is available. In the next few days, I will continue to discuss content from Neoplasms in my blogs.

-Jules Berman

Key words: tumors, tumour, neoplasms, neoplasia, carcinogenesis, tumor development, cancer research, neoplastic development, precancer preneoplasia, preneoplastic

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