Case 5 -
Anaplastic Large Cell Lymphoma (ALCL) Presenting in Bone Marrow
Chronic Idiopathic Myelofibrosis
University of New Mexico Health Sciences Center
Albuquerque, New Mexico
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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
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
case was kindly provided by Dr. R. Macaulay.
Key Discussion Points:
- Overview of ALCL
- ALK 1+ vs. negative ALCL
- ALCL in bone marrow, blood
- Features of current case
- ALCL mimicking chronic idiopathic myelofibrosis
- Morphology, IP of current case in bone marrow
- Overview of ALCL
Historical: Originally described in 1985 (Stein) as Ki 1 positive sinusoidal large cell lymphoma
Subsequent developments include:
Delineation of CP groups:
- 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-)
(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
||Common type (classic)|
- Neutrophil rich
- Eosinophil rich
||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-
Age (median) ||
60 yrs |
M/F ratio ||
B symptoms ||
Stage II/IV ||
BM involvement ||
5-yr survival ||
IP Comparison between systemic ALK 1+ and ALK 1- ALCL |
ALK 1+ ALCL, systemic ||
ALK 1- ALCL, systemic |
TIA 1 ||
bcl 2 ||
ALCL in Bone Marrow and Blood
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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