—  SPECIALTY CONFERENCE  —

Hematopathology

Case 5 - Anaplastic Large Cell Lymphoma (ALCL) Presenting in Bone Marrow Mimicking
Chronic Idiopathic Myelofibrosis

Kathryn Foucar
University of New Mexico Health Sciences Center
Albuquerque, New Mexico


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Clinical History:
68-year-old female with severe pancytopenia, hepatosplenomegaly, and recent onset of weakness, fever, weight loss, and confusion.

The patient has a past history of a cerebrovascular accident, multi-infarct dementia, hypertension, and congestive heart failure.

Diagnosis: Anaplastic large cell lymphoma presenting in bone marrow, mimicking chronic idiopathic myelofibrosis


Case 5 - Figure 1
Case 5 - Figure 2
Case 5 - Figure 3

Clinical Course:
During her brief disease course, the patient developed progressive liver failure, coagulopathy, and anemia. Fever persisted despite broad spectrum antibiotics; all cultures were negative. After diagnosis of ALCL all aggressive measures were discontinued and she expired.

Acknowledgement: This case was kindly provided by Dr. R. Macaulay.

Key Discussion Points:

  1. Overview of ALCL
  2. ALK 1+ vs. negative ALCL
  3. ALCL in bone marrow, blood
  4. Features of current case
    • ALCL mimicking chronic idiopathic myelofibrosis
    • Morphology, IP of current case in bone marrow
  1. Overview of ALCL Historical: Originally described in 1985 (Stein) as Ki 1 positive sinusoidal large cell lymphoma Subsequent developments include:
    • t(2;5)(p23;q35) in ALCL
    • Morphologic variants described (small cell, lymphohistocytic, sarcomatous)
    • Development of PCR techniques to detect fusion gene
    • Variant translocations identified
    • Monoclonal ALK 1 antibody for paraffin
    • ALK 1 staining pattern reflects genetics: NPM/ALK cases show nuclear/cytoplasmic positivity while variant translocations exhibit only cytoplasmic reaction
    • Other ALK 1+ (cytoplasmic) tumors described; inflammatory myofibroblastic tumor (CD30-)
    Delineation of CP groups:
    (ALCL constitutes about 5% of NHL in adults; 10-20% of pediatric NHL's and 30-40% of pediatric large cell lymphomas)
    • Cutaneous ALCL (ALK 1-): on spectrum with lymphomatoid papulosis
    • Primary systemic ALCL (ALK 1+)
    • Primary systemic ALCL (ALK 1-)
    • Other groups: secondary ALCL, HIV-related ALCL (ALK 1-)
    • ALK 1+ group homogeneous; ALK 1- group contains multiple entities

  2. Systemic ALCL
    Morphology: Common type (classic)
    Small cell
    Lymphohistiocytic
    Rare subforms:
    • Sarcomatoid
    • Neutrophil rich
    • Eosinophil rich
    • Signet-ring
    Typical IP/Genotype: CD30+, ALK 1+, CD45+, EMA+, TIA 1+, T-cell antigen variable (often + if several antibodies used), CD15- , EBER- , bcl 2-

    T-cell receptor gene rearrangement

    NPM/ALK positive (generally present), t(2;5) present

    Systemic ALK 1+ ALCL Systemic ALK 1- ALCL
    Age (median) 17yrs. 60 yrs
    M/F ratio 4-6:1 1:1
    B symptoms 40% 60%
    Stage II/IV 50% 65%
    BM involvement 10-20% 10-20%
    5-yr survival 75% 30%

    IP Comparison between systemic ALK 1+ and ALK 1- ALCL
    ALK 1+ ALCL, systemic ALK 1- ALCL, systemic
    CD30
    		 100% 100%
    EMA 95% 15-30%
    CD20 0 15%
    UCHL1 50% 50%
    CD4 50% 60%
    EBER 0 20-30%
    TIA 1 75% 10-30%
    bcl 2 0 60%

  3. ALCL in Bone Marrow and Blood

  4. Features of Current Case
    • Pancytopenia with rare tear drop RBC's
    • Inaspirable bone marrow—hypercellular, diffusely fibrotic with increased, clustered, atypical megakaryocytes and dilated sinuses
    • Large cells within dilated sinuses (both megakaryocytes and ALCL)
    • Vaguely nodular and dispersed, interstitial infiltrate of large multilobulated pleomorphic cells; occasional RS-like cells
    • IPox: striking diffuse and vaguely nodular increase in small CD3+ T cells. Large pleomorphic cells positive for CD45, CD3, CD30, CD4, and EMA, while these large cells are negative for ALK 1, CD15, CD20, CD8, TIA-1, and bcl 2. EBER is negative on decalcified core biopsy.
    • Cytogenetics: Normal karyotype on dilute bone marrow aspirate specimen (no particles)

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