An etiologic model proposing that sporadic adult-onset carcinoma is extramedullary hematopoiesis.
This model proposes that primary carcinomatous tumors and almost all metastases are extramedullary hematopoietic tissue formed to compensate for reduced hematopoietic activity in the bone marrow. These marrow lesions are currently considered to be metastatic in origin, but as fibrosis and sclerosis are identifying features they are here equated to myelofibrosis. Myelofibrotic marrow is characterized by an increase in the number and size of vascular sinusoids. The increased blood flow suggested by this morphology, and observed in myelofibrosis patients, causes a rise in marrow pressure which may trigger the fibrosis. Specific carcinoma morphologies are equated to stages in endochondral bone and marrow formation and, as such, cancer cell identity varies with morphology. For example, infiltrating carcinomas of the breast consist of collagen and mucoid secreting cells in single file formation. This morphology is equated to the cartilagenous stage of marrow formation, when mesenchymal stem cells proliferate and differentiate into chondroblasts. In this model "infiltrating" cells arise in situ from stem cells located in the connective tissue. Tubular breast carcinoma, with its single layer of osteoblast-like carcinoma cells encircling small lumens and long branching tubules, is equated to the trabecular stage of marrow formation during which osteoblasts surround small pieces of calcified cartilage and begin secreting osteoid that will form the trabeculae. Lobular carcinoma in situ consists of cancer cell clusters separated by narrow clear spaces that, under high magnification, appear vascular. This morphology is equated to hematopoietic tissue in which primitive hematopoietic cells lie between anastomosing sinusoids. Similar cartilagenous, trabecular and hematopoietic morphologies can be found in carcinomatous tumors of most organs, but the nomenclature is variable. The hematopoietic carcinomas share numerous features with hematopoietic tissue including a structure composed of intermingled normoxic and hypoxic regions and a metabolism characterized by elevated levels of glycolysis. They also contain similar proportions of clonal cells. If this model is correct it necessitates a change in the treatment of carcinoma. If cancer cells are not the enemy, but desperately needed immature blood cells, and the medical problem is not the presence of tumors, but the inefficiency of this extramedullary hematopoietic tissue, then treatment should focus on increasing marrow hematopoiesis. As evidence suggests that the marrow lesion is the result of increased hydrostatic pressure this could be done by reducing blood volume. One way to accomplish this may be through the ingestion of ephedrine, as it is hypothesized to increase vascular tone.
Schiel
Kathryn Ann
KA
kschiel@tvi.edu
D000328:Adult; D001854:Bone Marrow Cells; D002277:Carcinoma / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D006098:Granulocytes / Q000378:metabolism; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D008954:Models, Biological; D009362:Neoplasm Metastasis; D055728:Primary Myelofibrosis / Q000473:pathology