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INTRODUCTION

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SUMMARY

Myelophthisic anemia is caused by marrow infiltration, typically by metastatic cancer, and by any nonhematopoietic conditions, for example, granulomatous inflammation or fibrosis. It can present with an overt leukoerythroblastic picture or with only a few teardrop-shaped red cells on a blood film. These changes may represent an early spread of the tumor (or other nonhematopoietic tissue) to the marrow or may indicate massive replacement of the marrow space. The diagnosis can be made by standard marrow biopsy. Radioisotope scanning and magnetic resonance imaging, although not very sensitive, can be helpful in locating the biopsy site and can also help in estimating the percentage of involvement of the marrow space.

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Acronyms and Abbreviations:

MRI, magnetic resonance imaging; 99mTc, a radioisotope of technetium; 99mTc sestamibi, a radioisotope of technetium attached to the sestamibi molecule.

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DEFINITION AND HISTORY

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Myelophthisic anemia is the term that has been used to describe diverse pathologic processes, including Fanconi anemia,1 but currently refers to anemia resulting from the presence of spotty to massive marrow infiltration with abnormal cells or tissue components. Strictly speaking, the blasts of acute leukemia, plasma cells of myeloma, and cells of lymphoma, chronic leukemia, and myeloproliferative neoplasms fit this definition. However, the term myelophthisic anemia2 is best reserved for marrow replacement by nonhematologic tumors and nonhematopoietic tissue. Minimal to moderate involvement usually does not cause symptoms or hematologic changes. Such infiltration is clinically significant, however, because in patients with an established diagnosis of cancer, it indicates metastatic dissemination of the tumor and usually an advanced stage. Although extensive infiltration may lead to anemia or even pancytopenia, anemia can be frequently accompanied by an elevated leukocyte count, often with immature myeloid cells in the blood. Platelets can be increased, decreased, or normal (megakaryocytic fragments are seen occasionally in the blood film). The findings accompanied by teardrop-shaped red cells (dacrocytes), prematurely released nucleated red cells, and immature myeloid cells is referred to as leukoerythroblastic reaction (Chaps. 2, 31, and 86), which generally reflects marrow replacement by tumor or extramedullary hematopoiesis.

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ETIOLOGY AND PATHOGENESIS

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Tumor metastasis results from the complex interactions between the tumor cells and the surrounding microenvironment. Invasion is the primary process of metastasis and occurs often as a result of loss of E-cadherin. E-cadherin is a calcium-dependent cell adhesion molecule that likely plays a role in intercellular adhesion and inhibition of invasion by neoplastic cells. The loss of E-cadherin can be caused by many mechanisms, including mutations and gene silencing.3 Dysregulation of calcium influx pathways through stromal interaction molecule (STIM) and calcium-permeable transient receptor potential (TRP) also plays a role in tumor invasive and metastatic behavior.4 Many members of the family of matrix metalloproteinases can also participate in the process of tumor cell invasion. Stromal cells, such as tumor-associated macrophages, and growth factors secreted by them, such as ...

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