23-year-old man with lymphocytosis

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23-year-old man with lymphocytosis

Case 00-1

History/Physical Findings:

This 23-year-old man presented with a one-month history of fatigue, weakness, generalized body aches, intermittent fevers, night sweats and a ten-pound weight loss. Physical exam revealed cervical, supraclavicular and inguinal lymphadenopathy and a spleen palpable 2-3 cm below the costal margin.

Laboratory findings:

CBC on admission showed:

WBC

39.3 x 109/L

HGB

93 g/L

HCT

.29 L/L

PLT

152 x 109/L

Maximum white blood cell count on the 5th day of hospitalization was 111 x 109/L.

Peripheral Blood:

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Flow Cytometry of Peripheral Blood:

Bitmap 45% of all events- lymphocyte gate

CD19

2%

CD13

48%

CD20

1%

CD33

1%

CD10

2%

CD34

1%

Kappa

1%

CD56

5%

Lambda

1%

CD64

1%

CD2

12%

CD16

2%

CD3

2%

CD45

100%

CD5

2%

HLADR

43%

CD7

87%

MPO

3%

 

Flow cytometry reveals an abnormal population of CD45 bright cells which express CD7 and CD13 fails to express other T-cell markers. This profile is most consistent with an aberrant T-cell population.

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Lymph Node- H&E:

The cervical lymph node architecture is effaced by a nodular pattern separated by dense fibrous bands. The majority of cells are large, atypical lymphoid cells with abundant cytoplasm, nuclear folds and prominent nucleoli. A rare horseshoe nucleus is present. Mitoses are frequent.

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Lymph node- Immunohistochemistry:

The large, neoplastic cells show nuclear and cytoplasmic staining for Alk-1 and CD30 (Ki-1). T-cell markers CD43 and CD45RO (UCHL-1) are diffusely and focally positive respectively. CD45, CD20, 4KB5, CD3, CD5, CD15 and CD68 so not stain the large cells, but do show appropriate positivity in the tissue and make visible residual germinal centers.

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Bone Marrow:

The hypercellular marrow shows scattered atypical large cells that stained with CD30 and ALK-1.

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What is your diagnosis?

 

Discussion:

Anaplastic large cell lymphoma (ALCL) was first described in 1985 and was characterized by expression of Ki-1 (CD30), EMA and a null or T-cell phenotype. It was later recognized that tumors carrying the t(2;5)(p23;q35) translocation were CD30 positive large-cell lymphomas. This translocation fuses part of the nucleophosmin (NPM) gene on chromosome 5q35 to a portion of the ALK receptor tyrosine kinase on chromosome 2q23 to form a chimeric protein NPM-ALK. ALK-1 is a monoclonal antibody that is specific for the chimeric NPM-ALK protein and thus the t(2,5) translocation.

Four morphologic subtypes of ALK+ ALCLs have been described: common type, lymphohistiocytic, small-cell rich and giant-cell rich. More than one subtype can be found on a single biopsy or on repeat biopsies at time of relapse. All subtypes show the highly characteristic large cell, with an eccentric nucleus and an eosinophilic paranuclear region.

All diagnostic studies performed are consistent with the diagnosis of ALCL. Flow cytometry reveals an aberrant T-cell population with expression of CD7. The presence of CD13 is not uncommon in ALCL and is reported in up to 2/3 of cases. The architecture, cytology and immunohistochemistry of the lymph node are consistent with ALCL. Finally, the bone marrow shows the characteristic pattern of involvement, with scattered cells being picked up using CD30 and ALK-1. An unusual feature of this case is the leukemic presentation. All reported cases are of the small-cell variant and only the smaller cells are seen in the peripheral blood, as in this case.

 


Diagnosis:

 

Peripheral T-cell lymphoma, anaplastic large cell, Alk+ subtype.

 


 

References:

  1. Bayle C et al. Leukaemic presentation of small cell variant anaplastic large cell lymphoma: report of four cases. Brit J Haematol 104:680, 1999.
  2. Benharroch, D et al. ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood 91:2076, 1998.
  3. Villamor N et al. Anaplastic large-cell lymphoma with rapid evolution to leukemic phase. Ann Hematol 78:478, 1999.

 


 

Contributors:

Robin LeGallo, M.D.
Department of Pathology
University of Virginia Health Sciences Center

Donald J. Innes, Jr., M.D.
Department of Pathology
University of Virginia Health Sciences Center

Questions should be addressed to:

dji@Virginia.EDU