Bone marrow neoplastic
Myeloid
Acute leukemia-general


Topic Completed: 1 November 2013

Revised: 19 February 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed search: acute leukemia [title] bone

Sheren Younes, M.D.
Syed Zaidi, M.D.
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Cite this page: Younes S. Acute leukemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/boneacuteleukemia.html. Accessed April 3rd, 2020.
Definition / general
  • "Acute" because cells are immature (usually blasts) compared to mature hematopoietic cells in chronic leukemia
  • Also tend to progress rapidly without treatment, compared to indolent behavior of chronic leukemias
  • Acute Leukemia is a generalized myeloproliferative disorder and is divided into 2 categories:
    • Acute Myeloid Leukemia (AML), which arises from myeloid / granulocytic cell lines
      • Classified by French-American-British (FAB) system with M0 to M7 categories according to type of precursor
      • WHO classification incorporates molecular studies in AML classification
    • Acute Lymphoblastic Leukemia (ALL), which arises from lymphoid precursors
      • Either B or T cell
  • Acute leukemia often manifests with musculoskeletal disorders, which can mimic bone manifestations of other inflammatory diseases
Epidemiology
  • AML is most common type of leukemia in adults
  • ALL is most common in children although it has another peak after 65 years
  • Manifestations of bone involvement are more frequent in ALL (70%) than AML (15% - 20%)
  • Ionizing radiation is only definite environmental risk factor (Environ Health Perspect 2007;115:138)
Clinical features
  • General symptoms of leukemia are pallor, fatigue, bleeding, petichea, hepatosplenomegaly, lymphadenopathy, DIC
  • Local musculoskeletal symptoms arebone pain and gait disturbance, especially in long bones, described as sharp, intermittent, severe and sudden in onset
  • Vertebral body compression and pathological fracture
  • Joint pain (must distinguish from arthritis and similar inflammatory conditions)
  • Course of disease not affected by pregnancy (Cancer 2005;104:110)

Posttreatment:
  • Initially hypocellular with necrosis, proteinaceous debris, dilated sinuses and increased reticulin
  • Regeneration begins after 1 - 2 weeks
  • May be difficult to differentiate residual disease (tumor cells in no specific locations) from regenerating marrow (promyelocytes are perivascular and endosteal), particularly in acute promyelocytic leukemia
Laboratory
  • Usually elevated total leukocyte count, but could be normal or even reduced
  • Peripheral blood smear shows blasts
  • Also anemia, thrombocytopenia
  • Abnormal coagulation profile
  • Elevated LDH and uric acid
Diagnosis
  • Initial diagnosis usually based on blood counts and blood smear
  • Bone marrow examination (biopsy and smears) is necessary to confirm diagnosis and to obtain material for special studies
  • Bone marrow biopsy is essential to assess cellularity extent of involvement and to monitor posttreatment changes
  • Cytogenetics and molecular studies are required to classify and provide prognostic information
  • Before making a diagnosis, review clinical information, all pathology material and special studies
Radiology description
  • Osteolytic lesions, especially with ALL
    • At metaphyses of long bone
    • May occur in small and flat bones
  • Radiolucent metaphyseal bands (classic leukemia lines)
  • Diffuse osteopenia
  • Osteolysis, osteosclerosis or mixed pattern
  • Permeative bone destruction
  • Pathological fracture
  • Late radiologic lesions include vertebral collapse, osteolysis of talus and avascular osteonecrosis
Radiology images

AFIP images

Radiographic changes

Case reports
Treatment
  • Chemotherapy
  • Stem cell transplantation
Microscopic (histologic) description
  • AML:
    • Increased bone marrow cellularity, composed mainly of granulocytic or monocytic forms
    • Corresponding decrease in maturing granulocytic and monocytic forms
    • Variable number of erythroid precursors
  • ALL:
    • Hypercellular bone marrow
    • Numerous tightly packed lymphoblasts with undetectable cytoplasm, round, irregular, cleaved nuclei, dispersed chromatin, small nucleoli
    • B and T lymphoblasts are indistinguishable morphologically
    • Areas of necrosis
    • Expansile tumor mass can produce lytic bone lesions
    • May have granulomas associated with microorganisms
Microscopic (histologic) images

Images hosted on other servers:

ALL

Cytology description
  • AML:
    • More than 20% blasts, which may be myeloblasts, promyelocytes, monoblasts, promonocytes, promonocytes, megakaryoblasts
    • Erythroblasts are not included in blast count
    • Myeloblasts:
      • Large cells with moderate basophilic cytoplasm with azurophilic granules and Auer rods, single round / oval nuclei, fine chromatin, distinct nucleoli
      • Minimally differentiated AML has smaller myeloblasts
    • Monoblasts:
      • Large cells with abundant basophilic cytoplasm, azurophilic vacuoles, occasional granules and cytoplasmic blebbing; round nucleus, single prominent nucleolus
    • Promonocytes:
      • Abundant blue gray, sparsely granulated, often vacuolated cytoplasm; lobulated nuclei with delicate folds and creases
    • Megakaryoblasts:
      • Medium to large cells with round, irregular, occasionally bilobed nuclei with fine chromatin
    • Erythroblasts:
      • Medium to large cells with deeply basophilic cytoplasm, occasional granules containing PAS+ material; round nuclei, finely granular chromatin
  • ALL:
    • Increased lymphoid blast forms
    • Lymphoblasts have variable appearance:
      • Scant and basophilic cytoplasm, may have "hand mirror" cytoplasmic projections
      • Small homogenous cells with round slightly irregular nucleoli, condensed chromatin and inconspicuous nucleoli
      • Large heterogenous cells with irregular cleaved nuclei, variably distributed chromatin and distinct nucleoli
Peripheral smear description
  • Blasts >20%
  • Myoblasts in AML are:
    • Variably sized with abundant pale blue cytoplasm with azurophilic granules
    • Auer rods may be seen
    • Fine chromatin with distinct nucleoli
    • Blast counts in certain categories of AML may include monoblasts, megakaryoblasts, promonocytes and promyelocytes
    • Erythroblasts are excluded from the blast count
    • Three morphologic types of myeloblasts - Types I, II and III:
      • Type I myeloblasts contain no cytoplasmic granules
      • Type II myeloblasts contain 20% cytoplasmic azurophilic granules
      • Type III myeloblasts contain >20% cytoplasmic azurophilic granules
      • Lymphoblasts in ALL are small cells with scanty cytoplasm and indistinct nucleoli
  • Cytochemical and flow cytometry help distinguish different cell types
Immunohistochemistry
  • Immunostains should be ordered in panels (with multiple antigens) since aberrant antigen expression is common
  • Common lymphoid immunostains: TdT, T cell - CD2, CD3 (cytoplasmic), CD5, CD7; B cell - HLA-DR, CD10, CD19, CD22, CD79a (cytoplasmic), PAX5, CD20 (tissue sections)
  • Common myeloid immunostains: CD13, CD14, CD15, CD33, CD36, CD61, CD64
Positive stains
Negative stains
Flow cytometry description
  • Lineage specific markers distinguish AML and ALL and help diagnose different subtypes of acute leukemia
  • Count blasts to confirm the presence of 20% blasts
  • Useful to detect minimal residual disease
Molecular / cytogenetics description
  • Important for diagnostic, prognostic and therapeutic purposes
  • Routine karyotyping should be done in all acute leukemia cases
  • FISH or RT-PCR detect translocations
    • AML translocations include t(8;21), t(15;17), t(16;16), 11q23
    • ALL translocations include t(9;22), t(14;11)
Differential diagnosis
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