122 Abnormalities of the White Cell Series

Osteomyelosclerosis

When anemia accompanied by moderately elevated (although sometimes reduced) leukocyte counts, thrombocytopenia or thrombocytosis, clinically evident splenic tumor, left shift up to and including sporadic myeloblasts, and eosinophilia, the presence of a large proportion of red cell precursors (normoblasts) in the differential blood analysis, osteomyelosclerosis should be suspected. BCR-ABL gene analysis is negative.

Pathologically, osteomyelosclerosis usually originates from megakaryocytic neoplasia in the bone marrow and the embryonic hematopoietic organs, particularly spleen and liver, accompanied by fibrosis (= sclerosis) that will eventually predominate in the surrounding tissue. The central role of cells of the megakaryocyte series is seen in the giant thrombocytes, or even small coarsely structured megakaryocyte nuclei without cytoplasm, that migrate into the blood stream and appear in the CBC. OMS can be a primary or secondary disease. It may arise during the course of other myeloproliferative diseases (often polycythemia vera or idiopathic thrombocythemia).

Tough, fibrous material hampers the sampling of bone marrow material, which rarely yields individual cells. This in itself contributes to the bone marrow analysis, allowing differential diagnosis versus reactive fibroses (parainfectious, paraneoplastic).

Characteristics of OMS

Age of onset: Usually older than 50 years.

Clinical findings: Signs of anemia, sometimes skin irritation, drastically enlarged spleen.

CBC: Usually tricytopenia, normoblasts, and left shift.

Further diagnostic procedures: Fibrous bone marrow (bone marrow histology), when appropriate and BCR-ABL (always negative). Differential diagnosis: Splenomegaly in cases of lymphadenoma or other myeloproliferative diseases: bone marrow analysis. Myelofibrosis in patients with metastatic tumors or inflammation: absence of splenomegaly.

Course, therapy: Chronic disease progression; transformation is rare. If there is splenic pressure: possibly chemotherapy, substitution therapy.

Further myeloproliferative diseases are described together with the relevant cell systems: polycythemia vera (see p. 162) and essential thrombocythemia (see p. 170).

Enlarged spleen and presence of immature white cell precursors in peripheral blood suggest osteomyelosclerosis

a b

c d

Fig. 42 Osteomyelosclerosis (OMS). a and b Screening of blood cells in OMS: red cell precursors (orthochromatic erythroblast = 1 and basophilic erythroblast = 2), basophilic granulocyte (3), and teardrop cells (4). c Sometimes small, dense megakaryocyte nuclei are also found in the blood stream in myeloproliferative diseases. d Blast crisis in OMS: myeloblasts and segmented basophilic granulocytes (1).

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124 Abnormalities of the White Cell Series

Elevated Eosinophil and Basophil Counts

In accordance with their physiological role, an increase in eosinophils (#400/µl, i.e. for a leukocyte count of 6000, more than 8% in the differential blood analysis) is usually due to parasitic attack (p. 5). In the Western hemisphere, parasitic infestations are investigated on the basis of stool samples and serology.

Strongyloides stercoralis in particular causes strong, sometimes extreme, elevation of eosinophils (may be up to 50%). However, eosinophilia of variable degree is also seen in ameba infection, in lambliasis (giardiasis), schistosomiasis, filariasis, and even malaria.

Bacterial and viral infections are both unlikely ever to lead to eosinophilia except in a few patients with scarlet fever, mononucleosis, or infectious lymphocytosis. The second most common group of causes of eosinophilia are allergic conditions: these include asthma, hay fever, and various dermatoses (urticaria, psoriasis). This second group also includes druginduced hypersensitivity with its almost infinitely multifarious triggers, among which various antibiotics, gold preparations, hydantoin derivatives, phenothiazines, and dextrans appear to be the most prevalent. Eosinophilia is also seen in autoimmune diseases, especially in scleroderma and panarteritis. All neoplasias can lead to “paraneoplastic” eosinophilia, and in Hodgkin’s disease it appears to play a special role in the pathology, although it is nevertheless not always present.

A specific hypereosinophilia syndrome with extreme values (usually

#40%) is seen clinically in association with various combinations of splenomegaly, heart defects, and pulmonary infiltration (Loeffler syndrome), and is classified somewhere between autoimmune diseases and myeloproliferative syndromes. Of the leukemias, CML usually manifests moderate eosinophilia in addition to its other typical criteria (see p. 114). When moderate eosinophilia dominates the hematological picture, the term chronic eosinophilic leukemia is used. Acute, absolute predominance of eosinophil blasts with concomitant decrease in neutrophils, erythrocytes, and thrombocytes suggests the possibility of the very rare acute eosinophilic leukemia.

Elevated Basophil Counts. Elevation of segmented basophils to more than 2–3% or 150/µl is rare and, in accordance with their physiological role in the immune system regulation, is seen inconsistently in allergic reactions to food, drugs, or parasites (especially filariae and schistosomes), i.e., usually in conditions in which eosinophilia is also seen. Infectious diseases that may show basophilia are tuberculosis and chickenpox; metabolic diseases where basophilia may occur are myxedema and hyperlipidemia. Autonomic proliferations of basophils are part of the myeloproliferative

Eosinophilia and basophilia are usually accompanying phenomena in reactive and myeloproliferative disorders, especially CML

a
b
c	d

Fig. 43 Eosinophilia and basophilia. a Screening view of blood cells in reactive eosinophilia: eosinophilic granulocytes (1), segmented neutrophilic granulocyte (2), and monocyte (3) (reaction to bronchial carcinoma). b and c The image shows an eosinophilic granulocyte (1) and a basophilic granulocyte (2) (clinical osteomyelosclerosis). d Bone marrow in systemic mastocytosis: tissue mast cell (3), which, in contrast to a basophilic granulocyte, has an unlobed nucleus, and the cytoplasm is wide with a tail-like extension. Tissue mast cells contain intensely baso-

philic granules.

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126 Abnormalities of the White Cell Series

pathologies and can develop to the extent of being termed “chronic basophilic leukemia.” In the very rare acute basophilic leukemia, the cells in the basophilic granulocyte lineage mature in the bone marrow only to the stage of promyelocytes, giving a picture similar to type M3 AML (p. 98).

Being an expression of idiopathic disturbance of bone marrow function, elevated basophil counts are a relatively constant phenomenon in myeloproliferative syndromes (in addition to the specific signs of these diseases), especially in CML. Acute basophilic leukemia is extremely rare; in this condition, some of the dedifferentiated blasts contain more or less basophilic granules.

The tissue-bound analogs of the segmented basophils, the tissue mast cells, can show benign or malignant cell proliferation, including the (extremely rare) acute mast cell leukemia (Table 21).

Table 21 Different forms of benign and malignant proliferation of tissue mast cells

Clinical picture	Clinical diagnosis	Evidence
In childhood, solitary or	Localized mastocytosis	Histology
multiple skin nodules,
some brownish
"Sometimes transition
Diffuse brownish papules,	Urticaria pigmentosa	Typical clinical
with urticaria on irritation		picture
"
Hyperpigmented spots,	Systemic mastocytosis	Histology
papules and/or dermo-
graphism; histamine
symptoms: flushing, head-
ache, pruritus, abdominal
spasms, shock
"
Malignant transformation,	Malignant mastocyto-	Histology
possibly with osteolysis,	sis*
enlarged lymph nodes,
splenomegaly, hepa-
tomegaly
"
Migration of leukemic cells	Acute mast cell	CBC (bone marrow)
to peripheral blood	leukemia

* May occur de novo without preceding stages and without skin involvement.

Erythrocyte and Thrombocyte

Abnormalities