Continuing Education
CASE STUDIES IN ADULT NON-HODGKIN'S LEUKEMIA
CASE A:
A 50 year old, black female presented at an area hospital with abdominal pain and diarrhea. CT scan revealed an intra-abdominal mass with no disease above the diaphragm. Surgery was performed to remove the mass and lymph nodes. Staging biopsies were performed to determine the extent of disease. The results suggested kappa light chain restriction, but a definitive diagnosis of lymphoma was not rendered. The patient was treated with eight (8) cycles of chlorambucil and prednisone. The patient did well with no evidence of disease upon completion of therapy. After two (2) years, the patient presented at another area hospital with shortness of breath. Three taps on the pleural cavity were performed and were reported out as reactive lymphocytosis. The patient was released and referred to another area hospital, where the pleural cavity was tapped for a fourth time with the following results.
Chemistry: Cholesterol 108 mg/dL
Glucose 94 mg/dL
LD 326
IU/L
Protein 3.5 g/dL
Fluid Analysis: Color Cream
Clarity Turbid
RBC 1280
Nucleated
Cells 1920
Polys 2
Lymphs 95
Basos 1
Macros 2
Flow Cytometry: CD1 negative CD2 negative
CD3 negative CD4 negative
CD5 negative CD7 negative
CD8 negative CD10 dim
positive
CD19 positive CD20 positive
CD23 negative CD25 negative
CD45 positive MO2 negative
HLA-DR positive Skappa positive
Slambda negative
Cytogenetics: 46,XX,t(14;18)(q32;q21)
CASE B:
A 42 year old, HIV positive, white
male presented at a local cancer center with a rash and cervical lymphadenopathy. Biopsy results from the left cervical
lymph node are as follows.
Flow Cytometry: CD1% 0 CD2% 72
CD3% 72 CD4% 25
CD5% 75 CD7% 66
CD8% 44 CD10% 0
CD19% 24 CD20% 24
CD23% 8 CD25% 5
CD45% 100 MO2% 3
HLA-DR% 58 Skappa% 55
Slambda% 38
Anatomic Pathology/Immunopathology Special Stains:
L26 weakly
positive
LCA positive
CD30 equivocal
UCHL-1 negative in neoplastic cells
CD3 negative
in neoplastic cells
CD15 negative
in neoplastic cells
EMA negative
Kappa negative
Lambda negative
Cytogenetics: 82~88,XXXY,-X,-Y,+1,-1,+2,+2,+2,+2,add(2)(q?),+3,
-3,
-10,-10,+11,-11,-11,add(11)(q11),add(11)(p14),
-15,t(15;22)(p11;q11.2),
t(15;22)(p11;q11.2),-16,-16,-17,-17,
-17,-17,+18,-18,+19,-19,+20,-20,-21,-21,-21,-22,-22,
-22,+r(?),+r(?),+double r(?),+1~10mar[cp13]/46,XY[7]
ADULT NON-HODGKIN'S LYMPHOMA
Lymphomas are a diverse group of
malignancies. These malignancies have different behavior patterns and variably
respond to treatment. Lymphomas are classified into two (2) major families:
Hodgkin's Lymphomas (HL) and Non-Hodgkin's Lymphomas (NHL). Lymphomas, in
general, originate in lymphoid tissues and can matastasize
to other tissues. NHL is less predictable and has a greater tendency to
disseminate into extranodal sites. Relevant
prognostic factors for NHL and HL include histologic
subtype, stage, and response to treatment.
NHLs are
divided into two (2) distinct prognostic groups. Indolent NHL is defined by a
relatively good prognosis, and a median survival of approximately ten (10)
years. The morphology of most indolent NHLs is
nodular or follicular. Divergent histology of both indolent and aggressive
disease can increase the rate of relapse and have an adverse affect on the
patient's outcome.
Aggressive NHL is the second
prognostic group. The overall survival rate is five (5) years for roughly 50%
to 60% of these patients. Aggressive forms of NHL require intensive treatment
and are seen in increasing numbers in HIV-positive patients.
Lymphomas are classified according
to a number of different schemes. These schemes are often based on histology,
cell surface markers, cytogenetics, and gene
rearrangement analysis. These factors generally influence the diagnosis of,
prognosis for, and treatment of the patient. Lymph node biopsies are
recommended whenever possible because needle biopsies are sometimes
insufficient to identify the histologic type. The two
(2) most commonly used schemes for lymphoma classification are the REAL
(Revised European American Lymphoma) Classification and the ILSG (International
Lymphoma Study Group) Classification. The following tables outline these
classification schemes.
TABLE I: REAL CLASSIFICATION
SCHEME (Cannellos, et al., 1998)
B-Cell Neoplasms
Precursor B-Cell Neoplasm
Precursor B-Lymphoblastic
Leukemia/Lymphoma
Peripheral B-Cell Neoplasms
1.
B-Cell Chronic
Lymphocytic Lymphoma (CLL)/Prolymphocytic
Lymphoma (PLL)/Small Cell Lymphocytic
Lymphoma (SLL)
2.
Lymphoplasmacytoid Lymphoma/Immunocytoma
3.
Mantle Cell
Lymphoma
4.
Provisional
cytologic grades: I(small), II(mixed), III (large)
Provisional
subtype: diffuse, predominantly small cell
5.
Marginal Zone
B-Cell Lymphoma
Extranodal
(MALT + monocytoid B Cells)
6.
Provisional
Entity: Splenic Marginal Zone Lymphoma
7.
Hairy Cell
Leukemia
8.
Plasmacytoma/Myeloma
9.
Diffuse Large
B-Cell Lymphoma
10.
Burkitt's Lymphoma
11.
Provisional
Entity: High-Grade B-Cell Lymphoma, Burkitt's-like
T-Cell and Putative NK (Natural Killer)-Cell Neoplasms
Precursor T-Cell Neoplasm
Precursor T-Lymphoblastic
Leukemia/Lymphoma
Precursor T-Cell and
NK-Cell Neoplasms
1.
T-Cell CLL/PLL
2.
Large Granular
Lymphocytic Leukemia
3.
Mycosis Fungoides/Sézary's Syndrome
4.
Peripheral
T-Cell Lymphoma, Unspecified
Provisional
categories: medium, mixed, large, lymphoepitheliod
Provisional
subtypes: hepatosplenic gdT-Cell
Lymphoma
Subcutaneous panniculitic
T-Cell Lymphoma
5.
Adult T-Cell
Lymphoma/Leukemia
6.
Angioimmunoblastic T-Cell Lymphoma
7.
Angiocentric Lymphoma/Nasal T/NK-Cell Lymphoma
8.
Intestinal
T-Cell Lymphoma (+ enteropathy)
9.
Anaplastic Large Cell Lymphoma (T/Null)
10.
Provisional: Anaplastic Large Cell Lymphoma (ALCL) Hodgkin's-Like
Hodgkin's Disease
1.
Lymphocyte
Predominance (nodular + diffuse)
2.
Nodular
Sclerosis
3.
Mixed Cellularity
4.
Lymphocyte
Depletion
5.
Lymphocyte-rich
Classic HD (provisional subtype)
TABLE II: ILSG CLASSIFICATION
SCHEME (Cannellos, et al., 1998)
I.
Indolent Lymphomas and Lymphoid Leukemias
B-Cell
B-CLL/SLL
Lymphoplasmacytoid
lymphoma
Follicle center lymphoma, follicular
(small and mixed)
Marginal zone B-Cell lymphoma
Hairy cell leukemia
Plasmacytoma/myeloma
T-Cell
Large granular lymphocyte leukemia
ATL/L (smoldering)
Mycosis fungoides/Sézary's
Syndrome
II. Moderately Aggressive Lymphomas and Lymphoid Leukemias
B-Cell
B-PLL
Mantle cell lymphoma
Follicle center lymphoma (follicular
large cell)
T-Cell
T-CLL/PLL
ATL/L (chronic)
Angiocentric
lymphoma
Angioimmunoblastic
lymphoma
III. Aggressive Lymphoma
B-Cell
Large B-Cell lymphoma
T-Cell
Peripheral T-Cell lymphomas
Intestinal T-Cell lymphomas
Anaplastic
large cell lymphoma
IV. Highly Aggressive Lymphomas and Lymphoid Leukemias
B-Cell
Precursor B-lymphoblastic
leukemia (B-LBL)/lymphoma
Burkitt's
lymphoma
High-grade B-Cell lymphoma, Burkitt's-like
T-Cell
Precursor T-lymphoblastic
leukemia (T-LBL)/lymphoma
Adult T-Cell leukemia/lymphoma
(ATL/L) (acute and lymphomatous)
The
-unexplained loss of more than 10%
of body weight in the 6 months
before
diagnosis
-unexplained
fever with temperatures above 38°C
-drenching
night sweats
Stage I NHL means
involvement of a single lymph node region or localized involvement of a single
extra-lymphatic organ or site. Stage II means involvement of two (2) or more
lymph node regions on the same side of the diaphragm (II) or localized
involvement of a single associated extra-lymphatic organ or site and its
regional lymph nodes with or without other lymph node regions on the same side
of the diaphragm. The number of lymph node regions may be indicated by a
subscript (e.g., II3). Stage III NHL means involvement of lymph node regions on
both sides of the diaphragm that may also be accompanied by localized
involvement of an extra-lymphatic organ or site, by involvement of the spleen,
or both. Stage IV NHL means disseminated (multi-focal) involvement of one or
more extra-lymphatic sites with or without associated lymph node involvement or
isolated extra-lymphatic organ involvement with distant (non-regional) nodal
involvement. Current clinical practice assigns a clinical stage based on the findings
made as a result of invasive procedures beyond the initial biopsy (i.e., bone
marrow aspiration/biopsy, liver biopsy). (Cancernet,
1999)
Pathologic and clinical staging
relies on a number of laboratory analyses. Many of these analyses overlap with
chronic and acute lymphocytic leukemias.
The following tables outline possible results for the four most commonly used diagnositc tests, and associates these results with the
clinical symptoms and disease pheontype.