Page 32 - 2018_10-Haematologica-web

P. Valent et al.
physiological conditions such as pregnancy or advanced age.8,9,66,67 In these cases, the primary question is whether anemia is indicative of an undetected pathology and whether and when (at what thresholds) anemia can indeed be diagnosed. For example, in pregnant women, a hemoglobin level of 11.0 g/dL is still considered to be within the normal range by the World Health Organization (WHO). In elderly individuals, however, any decrease of hemoglobin below ‘normal’ is considered an anemia.8,9 On the other hand, there is an ongoing discus- sion about the definition of anemia in the elderly and related hemoglobin thresholds.9,68-70 When no evidence of an underlying condition is found after a thorough investi- gation of all relevant organs and potential etiologies, the condition is termed cytopenia (anemia) of unknown sig- nificance (ICUS-A).50,52 Thus, the diagnosis of ICUS-A implies that a detailed investigation of the bone marrow, with histological, morphological (cytological), immunophenotypic, cytogenetic and molecular studies, was performed without conclusive evidence of the pres- ence of MDS or any other underlying bone marrow neo- plasm.50,52 In this regard it is worth noting that next-gener-
ation sequencing may sometimes reveal more or less spe- cific mutations which may lead to re-classification of ICUS-A cases into either clonal cytopenia of undeter- mined significance or low-risk MDS, respectively.50-52 Other differential diagnoses to ICUS-A include anemia of chronic disease (inflammation-associated anemia), hemodilution, renal anemia, copper deficiency and vita- min B12 deficiency.9-11 In some elderly patients with ICUS- A, inadequately low levels of erythropoietin are found even though the excretory function of the kidney is nor- mal.71,72 In such cases, the aged kidney may be responsible for low erythropoietin production. Another equally important contributor to low red cell and erythropoietin production in elderly (otherwise healthy) people may be an age-related decrease in the production of hypophyseal and other essential hormones, resulting in a decreased supply of testosterone.73 However, unless an additional pathology (co-morbidity) is also present, these individuals have only mild anemia and are free of symptoms. As men- tioned, it remains uncertain as to whether all these elderly individuals should indeed be diagnosed as having overt anemia.
A
B
C
D
Figure 3. Structure and size of erythroid islands in the bone marrow. (A) Erythroid islands in the bone marrow of a 16-year old healthy male visualized by staining for CD71. (B) Erythroid islands in the bone marrow of an 82-year old female without bone marrow neoplasm. Erythroid islands were visualized by staining against hemo- globin A. Note the decreased number and increased size of erythroid islands in the bone marrow of the older healthy control. (C) Erythroid islands in the bone marrow of a 73-year old male patient with myelodys- plastic syndrome with excess of blasts (5- 9% of marrow cells, MDS-EB-1) visualized by staining for CD71. In the right images of 3A, 3B and 3C, erythroid islands are evi- denced by pink circles. Note the decreased number of erythroid islands in this patient. (D, left panel) Bone marrow section of a 78-year old male with myelodysplastic syn- drome with excess of blasts (10-19% of marrow cells, MDS-EB-2) stained for CD71. In this patient, numerous confluent, par- tially disrupted and poorly separable ery- throblastic islands are seen. (D, right panel) Bone marrow section of an adult patient with hemolytic anemia. Note that erythroid islands are increased, but are clearly separable and have a regular shape (contrasting with MDS). Original magnifica- tions: A, C, D: x 125; B: x 250.
1598
haematologica | 2018; 103(10)