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INTRODUCTION

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CASE HISTORY • Part 1

A 45-year-old man is referred by his orthopedic surgeon following the development of a pathological fracture of the neck of the femur after a fall on ice. X-rays taken at the time of the fracture show an abnormality of the ends of the long bones resembling an inverted Erlenmeyer flask.

The patient has otherwise been in good health. He is of Ashkenazi Jewish descent with a small family and is unaware of any genetic disorders in his family.

Examination is notable for an enlarged spleen, which is easily palpable several centimeters below the costal margin, and hepatomegaly. The remainder of his physical examination is normal.

His complete blood count (CBC) is normal with the exception of a moderately reduced platelet count of 80,000/μL.

Questions
  • Given this limited amount of information, what diagnoses come to mind?

  • What additional tests and procedures are necessary to evaluate this patient?

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The mature cells that comprise the monocyte-macrophage system function both as phagocytes and as antigen-presenting cells. Disorders of the monocyte/macrophage lineage are quite heterogeneous and include "benign" disorders such as Langerhans-cell histiocytosis, reactive histiocytosis, and the lysosomal storage diseases, as well as monocytic and histiocytic malignant proliferations. In naming these disorders, the term "histiocyte" is used interchangeably with "macrophage" to describe the tissue-bound phagocytic cells found throughout the body.

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The morphologic appearance of the tissue macrophage is key to the differential diagnosis of these disorders. For example, reactive histiocytosis is characterized by prominent monocytosis and a tissue granulomatous reaction typical of the normal role of macrophages in host defense against infection. The so-called storage diseases are a manifestation of genetic deficiencies of certain enzymes responsible for the degradation of carbohydrates and lipids. Even though these enzyme deficiencies presumably affect all the cells in the body, the characteristic abnormality is an accumulation of degraded cellular debris within tissue macrophages. Primary malignancies of the tissue macrophages are quite rare; marrow and tissue invasion by erythrophagocytic histiocytes is a primary distinguishing feature of such malignancies.

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THE NORMAL MONOCYTE-MACROPHAGE SYSTEM

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As with the other hematopoietic cell lines, the monocyte-macrophage cell lineage arises from the common hematopoietic stem cell. Cell differentiation and maturation to form mature circulating monocytes is under the control of granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and monocytic colony-stimulating factor (M-CSF). Two distinct categories of blood monocytes are recognized according to their phenotypic expression. All monocytes display CD14, and the majority are CD16, whereas 10% are more mature and express CD16+ together with class II major histocompatibility complex (MHC) molecules and adhesion molecules such as CCR2 and CX3CL1 (see Chemokines and Their Receptors in Chapter 16). These "mature" monocytes synthesize proinflammatory cytokines such as interleukin [IL]-1, IL-6, tumor necrosis factor [TNF]-α and IL-12. When activated, monocytes also play a role in coagulation and fibrin deposition at inflammatory sites, through expression of tissue ...

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