University of Virginia Health System

Acute Monoblastic Leukemia
(M5 AML, Schilling's acute monoblastic leukemia, AMoL)

(a) M5a AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(b) M5b AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(c) M5 AML (AMoL)- Bone marrow aspirate smear, non-specific esterase (NSE) stain, 1000x 

Description

This subtype represents up to 9% of all AMLs in adults. Two morphologic variants are recognized, M5a (without differentiation) and M5b (with differentiation). The FAB criterion for a diagnosis of M5a AML is that 80% or more of the nonerythroid cells on a bone marrow aspirate be monoblasts, promonocytes and monocytes; this criterion does not become an issue in most cases. The predominant cell present is a monoblast with little to no differentiation. The blasts vary in size, but most are about 1½ - 2 times the size of a normal segmented neutrophil. The cytoplasm is abundant although the nuclear:cytoplasmic ratio does vary, and the color ranges from a medium to dark blue, and granules usually are not visible. Vacuoles may be seen. Auer rods are not seen. The nucleus varies slightly in size and shape, the chromatin is fine and light staining with one or more prominent nucleoli may be visible. The M5a variant is seen more in younger adults.

In the M5b variant there is both nuclear and cytoplasmic maturation. The size and shape of the blasts are more variable than in the M5a variant. The cytoplasm is more abundant, is light blue to blue-grey in color, and contains fine granules that have a "salt and pepper" appearance. Vacuoles are more prominent than in the M5a variant. The nucleus frequently has a convoluted appearance and both the size and shape vary. The nuclear chromatin is often more clumped and one or more prominent nucleoli are visible, but to a lesser degree than in the M5a variant.

Cytochemistry:

In the M5a variant, the non-specific esterase (NSE) is positive (c), and myeloperoxidase (MPO) and Sudan black B are negative. In addition to a positive MSE stain, the Sudan black B may be positive in M5b variant.

Immunophenotype:

• Stem cell and hematopoietic progenitor cell markers- CD34-, HLA-DR -
• Monocytic lineage markers- CD14±, CD116±, CD11c±, CD64±, CD68±, CD4±, and lysozyme±
• Myeloid lineage markers- CD33±, CD13±, CD117±

Note: In general the M5b subtype shows more positivity with more mature monocyte markers.

Cytogenetics:

Cytogenetic abnormalities are found in most cases, but a signature abnormality has not been identified. Abnormalities involving the 11q23 are not infrequent, including those cases that occur following exposure to the topisomerase II inhibitors (VP-16 and VM-26).

Clinical and Laboratory Manifestations:

In addition to those listed for acute leukemias in general, patients with M5 AML, especially the M5b variant, have more involvement of other organs, e.g. gums, skin (leukemia cutis), meninges, liver and spleen, similar to the M4 AMLs. Leukostasis occurs at a lower peripheral blood blast count. Evidence of DIC at diagnosis is relatively common. This subtype is the most frequent one seen following the exposure to the topoisomerase II inhibitors (VP-16 and VM-26).

Prognosis:

Poor, especially in the M5a variant.

General References:

• Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Pathology and genetics of tumors of hematopoietic and lymphoid tissues. Vol. 3 of World Health Organization classification of tumors, Lyon, France: IARC Press, 2001
• Watkins CH, Hall BE: Monocytic leukemia of the Naegeli and Schilling types. Am J Clin Pathol 10:387, 1940
• Scott SS, Stark AN, Limbert HJ, et al: Diagnostic and prognostic factors in acute monocytic leukemia: Analysis of 51 cases. Br J Haematol 69:247, 1988
• Fung H, Shepherd JD, Naimon SC et al: Acute monocytic leukemia: A single institution experience. Leuk Lymphoma 19:259, 1995

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