Bone marrow neoplastic

• Highly aggressive neoplasm of precursor lymphoid (blast) cells
• 2 main subtypes based on lymphoid lineage
  • B lymphoblastic leukemia / lymphoma (B-ALL / LBL)
  • T lymphoblastic leukemia / lymphoma (T-ALL / LBL)

• Bone marrow, peripheral blood or nodal involvement
• Anterior mediastinum
  • Particularly T-LBL
  • Compromised cardiac function and superior vena cava syndrome may result
• Less frequent sites involved
  • Skin
  • Soft tissues
  • Central nervous system

• Idiopathic and likely multifactorial
• Chromosomal aberrations with gene mutations and rearrangements commonly cited
• Specific risk factors seen in a minority of patients:
  • Prenatal radiation exposure (Xradiation)
  • Postnatal exposure to high doses of radiation (e.g. therapeutic radiation was previously used for tinea capitis and thymus enlargement)
  • Genetic conditions, such as Down syndrome, neurofibromatosis and ataxia telangiectasia
  • Inherited genetic polymorphisms
• Reference: Swerdlow: WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues (Medicine), 4th Edition, 2017

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• In tissue masses or marrow, effacement of architecture by round blue cells raises the differential diagnoses of ALL / LBL versus neuroblastoma, Ewing sarcoma and other mimickers
• Proliferation of typically small to medium sized primitive cells but some tumor cells may appear as larger blasts containing cytoplasmic vacuoles
• B and T cell precursors are morphologically indistinguishable
• In nodal involvement, blasts usually display a diffuse growth pattern
  • Partial nodal involvement of T-LBL may have a predominantly interfollicular distribution
  • Lymphoblasts may be oval in shape and display an indented nucleus with finely dispersed chromatin and inconspicuous nucleoli
• Revised criteria to the original French American British (FAB) classification of ALL cytologic subtypes
  • L1 and L2 subtype segregation not shown to correlate with clinical or biologic behavior; thus, most commonly used for descriptive purpose at this time
    • L1 subtype: most common, with intermediate size, uniform features, scant basophilic cytoplasm, slightly condensed chromatin with inconspicuous / absent nucleoli
    • L2 subtype: more heterogeneous appearance, with slightly more cytoplasm and more prominent nucleoli, resembling myeloblasts
    • L3 subtype: now corresponds to leukemic phase of Burkitt lymphoma, a high grade mature B cell lymphoma (Blood Cancer J 2017;7:e577)

Contributed by Patricia Tsang, M.D.

Contributed by Patricia Tsang, M.D.

Contributed by Patricia Tsang, M.D.

• Burkitt lymphoma, a high grade B cell lymphoma:
  • In BL, there is typically monotypic surface immunoglobulin light chain expression
  • Starry sky histologic pattern and cytoplasmic vacuoles on smear or touch preparation
  • Unlike B-ALL / LBL, its phenotype is mature showing consistent CD20 but without CD34 or TdT expression
• Hematogones, non-clonal B cell precursors in bone marrow, can be confused with B-ALL, especially in minimal residual disease:
  • Typically smaller than lymphoblasts
  • Have characteristic immunophenotypic expression pattern by flow cytometry
• Thymoma with reactive thymic T cells exhibiting CD4+ CD8+ immature T cell phenotype, resembling T-LBL in anterior mediastinal mass:
  • Immunohistochemistry highlights the neoplastic epithelial cell component
  • Lobulated architecture
  • May be associated with myasthenia gravis in adults
• Incidental indolent T lymphoproliferative proliferations (Cytometry B Clin Cytom 2020;98:282)

A 4 year old boy is brought to the physician by his mother due to a 5 week history of lethargy, a progressively enlarging left sided neck mass and a 5 day onset of unexplainable bilateral diffuse lower leg petechial hemorrhage. On exam, the left posterior cervical lymph node is enlarged and nontender to palpation. A lymph node biopsy shows a predominance of interfollicular infiltrate containing numerous blast cells and focal necrosis. Immunohistochemistry is positive for PAX5, CD10 and TdT. Upon further workup, which of the following translocations would be associated with a good prognosis?

1. t(12;21)
2. t(14;18)
3. t(8;14)
4. t(9;22)

A. t(12;21)

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Reference: Acute lymphoblastic leukemia / lymphoblastic lymphoma

A 58 year old Hispanic woman comes to the physician because of a 2 month history of bilateral axillary lymphadenopathy and a new onset right breast mass at 12 o'clock. The patient has a previous history significant for Down syndrome and a diagnosis of acute lymphoblastic leukemia 20 years ago for which she received treatment and has since been free of disease. Needle core biopsy of the breast mass reveals extensive involvement by monotonous medium sized lymphoid cells with a high N/C ratio and scant cytoplasm, consistent with a diagnosis of B lymphoblastic lymphoma. Which of the following genetic mutations is most likely detected in blast cells?

1. BCR-ABL1
2. CRLF2
3. ETV6-RUNX1
4. FLT3

B. CRLF2

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Reference: Acute lymphoblastic leukemia / lymphoblastic lymphoma