Chapter 35: Monocytosis and Monocytopenia

• Monocytes in the blood are in transit. They function in the tissues, where they mature into macrophages and participate in:

  — Inflammation, including granulomatous reactions, atheroma formation, and tissue repair

  — Immunologic reactions, including delayed hypersensitivity

  — Reactions to neoplasia and allografts

• The need for macrophages in tissues also can be met by local proliferation of macrophages, not requiring increased transit of blood monocytes.

• Ninety percent of blood monocytes intensely express CD14 (lipopolysaccharide receptor) but not CD16 (Fc receptor) and 10% have weak expression of CD14 and strongly express CD16.

• Older persons have a striking decrease in the proportion of CD14++CD16– to CD14+CD16+ monocytes compared with younger persons.

• Disorders rarely produce abnormalities of monocytes alone in the absence of other blood cell abnormalities.

• The monocyte count averages 1.0 × 10⁹/L in neonatal life, gradually decreasing to a mean of 0.4 × 10⁹/L in adult life.

• Monocytosis (in adults) is greater than 0.8 × 10⁹/L.

• Monocytopenia is less than 0.2 × 10⁹/L.

• See Table 35–1.

Neoplastic or Clonal Monocytic Proliferations

• Oligoblastic myelogenous leukemia (refractory leukemia with excess blasts or myelodysplastic syndrome)

• Acute myelogenous leukemia (myelomonocytic or monocytic types)

• Chronic myelomonocytic leukemia

• Juvenile myelomonocytic leukemia

• Unusual type of BCR-ABL (p190)-positive chronic myelogenous leukemia with monocytosis

Reactive (Nonclonal) Monocytic Proliferations

• Neutropenic states: cyclic neutropenia; chronic granulocytopenia of childhood; familial benign neutropenia; infantile genetic agranulocytosis; chronic hypoplastic neutropenia

• Drug-induced agranulocytosis (transient monocytosis, especially in the recovery phase)

• Chlorpromazine toxicity, monocytosis preceding the agranulocytosis

• Lymphoma

• Hodgkin lymphoma

• Postsplenectomy state

• Myeloma

• See Table 35–1.

Collagen Vascular Diseases

• Rheumatoid arthritis

• Systemic lupus erythematosus

• Temporal arteritis

• Myositis

• Polyarteritis nodosa

Chronic Infections

• Bacterial infections (eg, subacute bacterial endocarditis, tonsillitis, dental infections, recurrent liver abscesses [probably not in typhoid fever or brucellosis])

• Tuberculosis

• Syphilis: neonatal, primary, and secondary

• Viral infections: cytomegalovirus and varicella-zoster virus

Other Inflammatory Disorders

• Sprue

• Ulcerative colitis

• Regional enteritis

• Sarcoidosis (the degree of monocytosis is inversely related to reduction in number of T lymphocytes)

• Found in about 20% of patients who have monocytosis; independent of metastatic disease

• Alcoholic liver disease

• Tetrachloroethane poisoning

• Langerhans cell histiocytosis

• Parturition

• Severe depression

• See Table 35–1

• Aplastic anemia

• Hairy cell leukemia:

  — May be a helpful diagnostic clue

  — Contributes to the frequent infections

• Chronic lymphocytic leukemia

• Cyclic neutropenia

• MonoMAC syndrome

  — Caused by GATA2 mutations

  — Autosomal dominant

  — May be sporadic event

  — Severe monocytopenia (to amonocytosis)

  — B-lymphocytopenia and natural killer cell cytopenia

  — Predisposition to mycobacterial, fungal, human papilloma virus, and Epstein-Barr virus infections

  — Predisposed to develop myelodysplasia or acute myelogenous leukemia

  — Predisposed to develop vulvar carcinoma, metastatic melanoma, cervical carcinoma, Bowen disease of the vulva, and leiomyosarcoma

• Severe thermal injury

• Rheumatoid arthritis

• Systemic lupus erythematosus

• HIV infections

• Postradiation therapy

• Following the administration of:

  — Glucocorticoids

  — α-Interferon

  — Tumor necrosis factor-α

• Blood dendritic cells are composed of two phenotypic subtypes: myeloid-derived (HLA-Dr+CD11c+CD123+) and lymphoid-plasmacytoid-derived (HLA-Dr+CD11c–CD123+).

• The total blood dendritic cell count can be measured by flow cytometry.

• Dendritic cells make up approximately 0.6% of blood cells (range: 0.15%–1.30%) and represent 14 × 10⁶ cells/L (range: 3 to 30 × 10⁶ cells/L). Approximately one-third of these cells are lymphoid-plasmacytoid–derived type and two-thirds are myeloid-derived type.

• Blood dendritic cell counts decrease with aging and increase with surgical stress (and presumably other stressful reactions) in relation to plasma cortisol levels.

• Fluctuations in blood dendritic cells are often independent of changes in blood monocyte counts.