Chloniak_nieziarniczy

Non-Hodgkin Lymphoma
Protocol applies to non-Hodgkin lymphoma
involving any organ system except the
gastrointestinal tract.
Protocol revision date: January 2004
Procedures
• Cytology (No Accompanying Checklist)
• Biopsy
• Resection of Lymph Node or Other Organ

Authors
Carolyn Compton, MD, PhD
Department of Pathology, McGill University, Montreal, Quebec, Canada Department of Pathology, UCLA School of Medicine, Los Angeles, California For the Members of the Cancer Committee, College of American Pathologists
Previous contributors: Nancy L. Harris, MD; Dennis W. Ross, MD, PhD; Annik van
den Abbeele, MD; Judith Ferry, MD; Claire Fung, MD; Irene Kuter, MD; Peter Mauch,
MD
Non-Hodgkin Lymphoma • Hematologic System
CAP Approved
Surgical Pathology Cancer Case Summary (Checklist)
Protocol revision date: January 2004 Applies to non-gastrointestinal, non-Hodgkin lymphoma only
NON-HODGKIN LYMPHOMA: Biopsy/Resection

Patient name:
Surgical pathology number:

Note: Check 1 response unless otherwise indicated.

MACROSCOPIC
Specimen Type
___ Lymphadenectomy
___ Other (specify): ____________________________
___ Not specified
Tumor Site (check all that apply)
___ Lymph node(s), site not specified ___ Lymph node(s) Specify site(s): _______________________________________ ___________________________________________________ Specify site(s): _______________________________________ ___________________________________________________ ___ Not specified
MICROSCOPIC
Histologic Type (WHO Classification)
___ Histologic type cannot be assessed
B-cell Lymphoma
___ B-cell lymphoma, subtype cannot be determined
___ Precursor B-lymphoblastic leukemia/lymphoma
___ Chronic lymphocytic leukemia/small lymphocytic lymphoma
___ B-cell prolymphocytic leukemia
___ Lymphoplasmacytic lymphoma
___ Splenic marginal zone lymphoma
___ Hairy cell leukemia
___ Plasma cell myeloma/ Plasmacytoma
* Data elements with asterisks are not required for accreditation purposes for
the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen. CAP Approved
Hematologic System • Non-Hodgkin Lymphoma
___ Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue * Data elements with asterisks are not required for accreditation purposes for
the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen. Non-Hodgkin Lymphoma • Hematologic System
CAP Approved
___ Nodal marginal zone B-cell lymphoma ___ Follicular lymphoma, grade 1 (0-5 centroblasts per HPF) ___ Follicular lymphoma, grade 2 (6-15 centroblasts per HPF) ___ Follicular lymphoma, grade 3 (greater than 15 centroblasts per HPF) ___ Follicular lymphoma, cutaneous follicle center sub-type ___ Follicular lymphoma, diffuse follicle center sub-type, grade 1 ___ Follicular lymphoma, diffuse follicle center cell sub-type, grade 2 ___ Mantle cell lymphoma
___ Diffuse large B-cell lymphoma
___ Mediastinal (thymic) large B-cell lymphoma
___ Intravascular large B-cell lymphoma
___ Primary effusion lymphoma
___ Burkitt lymphoma/leukemia
___ Lymphomatoid granulomatosis
___ Other (specify): ____________________________
T-cell Lymphoma
___ T-cell lymphoma, subtype cannot be determined
___ Precursor T-lymphoblastic leukemia/lymphoma
___ T-cell prolymphocytic leukemia
___ T-cell large granular lymphocytic leukemia
___ Aggressive NK-cell leukemia
___ Adult T-cell leukemia/lymphoma
___ Extranodal NK/T-cell lymphoma, nasal type
___ Enteropathy-type T-cell lymphoma
___ Hepatosplenic T-cell lymphoma
___ Subcutaneous panniculitis-like T-cell lymphoma
___ Mycosis fungoides / Sézary syndrome
___ Primary cutaneous anaplastic large cell lymphoma
___ Peripheral T-cell lymphoma, unspecified
___ Angioimmunoblastic T-cell lymphoma
___ Anaplastic large cell lymphoma
___ Lymphomatoid papulosis
___ Other (specify): ____________________________
Extent of Pathologically Examined Tumor (check all that apply)
___ Involvement of a single lymph node region
Specify site: ____________________________ ___ Involvement of multiple lymph node regions Specify: _______________________________ ___ Splenic involvement ___ Liver involvement ___ Bone marrow involvement ___ Other organ involvement Specify: ________________________________ * Data elements with asterisks are not required for accreditation purposes for
the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen. CAP Approved
Hematologic System • Non-Hodgkin Lymphoma
* Data elements with asterisks are not required for accreditation purposes for
the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen. Non-Hodgkin Lymphoma • Hematologic System
CAP Approved
Phenotyping
___ Performed, see separate report
___ Performed
Specify method and results: ______________________________ __________________________________________________ ___ Not performed
*Additional Pathologic Findings
*Specify: _______________________________________
*Comment(s)

* Data elements with asterisks are not required for accreditation purposes for
the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen. For Information Only
Hematologic System • Non-Hodgkin Lymphoma
Background Documentation
Protocol revision date: January 2004
I. Cytologic Material
A. Clinical Information
a. Name
b. Patient identification number
c. Age (birth date) (Note A)
d. Sex (Note B)
2. Responsible physician(s) 3. Date of procedure 4. Other clinical information a. Relevant history (eg, duration of lymphadenopathy or other mass; previous diagnosis and treatment for lymphoma, Hodgkin lymphoma, or other malignancy; immunosuppression; AIDS; bone marrow or solid organ transplantation) b. Relevant findings (eg, distribution of lymphadenopathy, signs and symptoms, imaging studies, serum lactate dehydrogenase [LDH] level)
(Note C)
c. Clinical diagnosis
d. Clinical stage, if known
e. Specific procedure (fine-needle aspiration [FNA], tap of effusion, other)
f. Operative findings
g. Anatomic site(s) of specimen(s) (Note D)
B. Macroscopic Examination
a. Unfixed/fixed (specify fixative) b. Number of slides received, if appropriate c. Quantity and appearance of fluid specimen, if appropriate d. Other (eg, cytologic preparation from tissue) e. Results of intraprocedural consultation 2. Material submitted for microscopic evaluation (eg, FNA, cytospin of fluid, other) 3. Special studies, specify (eg, flow cytometry for immunophenotyping, cytochemistry, immunohistochemistry, cytogenetic analysis) C. Microscopic Evaluation
1. Adequacy of specimen (if unsatisfactory for evaluation, specify reason) 2. Lymphoma, if present a. Histologic type, if possible (Note E)
b. Other characteristics (eg, necrosis)
3. Additional pathologic findings, if present 4. Results /status of special studies (specify) 5. Comments a. Correlation with intraprocedural consultation, as appropriate b. Correlation with other specimens, as appropriate c. Correlation with clinical information, as appropriate Non-Hodgkin Lymphoma • Hematologic System
For Information Only
II. Biopsy
A. Clinical Information
a. Name
b. Patient identification number
c. Age (birth date) (Note A)
d. Sex (Note B)
2. Responsible physician(s) 3. Date of procedure 4. Other clinical information a. Relevant history (eg, duration of lymphadenopathy or other mass; previous diagnosis and treatment for lymphoma, Hodgkin lymphoma, or other malignancy; immunosuppression; AIDS; bone marrow or solid organ transplantation) b. Relevant findings (eg, distribution of lymphadenopathy, signs and symptoms, imaging studies, serum LDH level) (Note C)
c. Clinical diagnosis
d. Clinical stage, if known
e. Specific procedure (eg, lymph node biopsy, liver biopsy)
f. Operative findings
g. Anatomic site(s) of specimen(s) (Note D)
B. Macroscopic Examination
a. Unfixed/fixed (specify fixative) (Note: When appropriate, fresh sterile tissue should be sent for culture, and fresh frozen tissue should be saved, if possible, for immunophenotyping and molecular genetic studies) b. Number of pieces c. Largest dimension of each piece d. Results of intraoperative consultation 2. Submit nonfrozen tissue for microscopic evaluation 3. Special studies, specify (eg, flow cytometry for immunophenotyping, cytochemistry, immunohistochemistry, cytogenetic analysis) (Note F)
C. Microscopic Evaluation
a. Histologic type (Note E)
b. Other characteristics (eg, necrosis)
2. Additional pathologic findings, if present 3. Results/status of special studies 4. Comments a. Correlation with intraoperative consultation, as appropriate b. Correlation with other specimens, as appropriate c. Correlation with clinical information, as appropriate
III. Resection of Lymph Node or Other Organ
A. Clinical Information
a. Name
b. Patient identification number
c. Age (birth date) (Note A)
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Hematologic System • Non-Hodgkin Lymphoma
d. Sex (Note B)
2. Responsible physician(s) 3. Date of procedure 4. Other clinical information a. Relevant history (eg, duration of lymphadenopathy or other mass; previous diagnosis and treatment for lymphoma, Hodgkin disease, or other malignancy; immunosuppression; AIDS; bone marrow or solid organ transplantation) b. Relevant findings (eg, distribution of lymphadenopathy, signs and symptoms, imaging studies, serum LDH level) (Note C)
c. Clinical diagnosis
d. Clinical stage, if known
e. Specific procedure (eg, lymph node excision, splenectomy, other)
f. Operative findings
g. Anatomic site(s) of specimen(s) (Note D)
B. Macroscopic Examination
a. Organ(s)/tissue(s) (Note D)
b. Unfixed/fixed (specify fixative) (Note: When appropriate, fresh sterile tissue
should be sent for culture and fresh frozen tissue should be saved for immunophenotyping and molecular genetic studies) c. Number of pieces d. Dimensions e. Orientation of specimen, if indicated by surgeon f. Results of intraoperative consultation a. Number of lesions (Note G)
b. Location (Note G)
c. Configuration
d. Dimensions
e. Descriptive characteristics (eg, color, consistency)
f. Direct extension to other organ(s) or structure(s) (Note H)
g. Noncontiguous tumor involvement of other organ(s) or structure(s) (Note G)
3. Other lesions 4. Tissues submitted for microscopic evaluation a. Lymphoma, representative sections b. Other specific nodes, when marked by surgeon c. Other lesions d. Section(s) of tissue uninvolved by tumor e. Other tissue(s)/organ(s) 5. Special studies, specify (eg, flow cytometry for immunophenotyping, cytochemistry, immunohistochemistry, cytogenetic analysis) (Note F)
a. Histologic type (Note E)
b. Direct extension to other organ(s) or structure(s)
2. Additional pathologic findings, if present (eg, reactive follicular hyperplasia) 3. Other tissues submitted (if distant involvement by lymphoma, specify site) Non-Hodgkin Lymphoma • Hematologic System
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4. Results/status of special studies (specify) 5. Comments a. Correlation with intraoperative consultation, as appropriate b. Correlation with other specimens, as appropriate c. Correlation with clinical information, as appropriate
Explanatory Notes
A. Patient Age
Age is a risk factor independently associated with survival in non-Hodgkin lymphoma
(NHL). Age above 60 years has been shown to be associated with decreased survival
compared to age 60 or less.1-4 In some series of patients with low grade NHL, age
greater than 40 has been associated with decreased survival.5 Across all grades and
stages of NHL, a decreased ability of patients greater than 60 years of age to tolerate
treatment may be the major effect of age.3 However, even among patients treated
equivalently for low stage disease (ie, stage I and II, see below), older patients are at
greater risk for relapse than younger patients.3,6-16
B. Sex
Across all grades and stages of NHL, male sex has been shown to correlate with other
adverse prognostic factors such as histologic type, stage, and symptoms (see below).
However, it has also been demonstrated to have independent adverse prognostic
significance in patients with low grade NHL.5,14,17
C. Clinical Findings
Although not always provided to the pathologist by the physician submitting the
specimen, certain specific clinical findings are known to be of prognostic value in NHL
(across all stages). In particular, systemic symptoms of fever (greater than 38.5°C),
unexplained weight loss (more than 10% body weight) in the 6 months before
diagnosis, and drenching night sweats are used to define 2 categories for each stage
of NHL: A (symptoms absent), and B (symptoms present). The presence of B
symptoms is known to correlate with extent of disease (stage and tumor bulk), but
symptoms also have been shown to have prognostic significance for cause-specific
survival that is independent of stage.3,4,6,13,18,19
Poor patient “performance status” has also been shown by several multivariate
analyses to have independent adverse prognostic significance.1,6,10,17 Performance
status refers to the overall activity level of the patient ranging from fully active to
completely bed-ridden, and a poor performance status is usually defined as any degree
of activity less than fully active or fully ambulatory (ie, bed-ridden for varying
proportions of time).1,2
Elevated serum lactate dehydrogenase (LDH) level is an adverse prognostic factor that
correlates with tumor burden (stage and bulk).3 It has also been shown to have
independent prognostic significance in both early and late stage NHL in many
studies.8,12,16,20-25
Tumor bulk, usually defined by clinical and/or imaging studies, is a predictive factor in
various settings.3 A tumor greater than 5 to 10 cm in diameter is associated with higher
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Hematologic System • Non-Hodgkin Lymphoma
rates of relapse of stage I and II NHL treated with radiotherapy.13 A tumor greater than
10 cm in diameter is associated with poor outcome in patients with stage III and IV NHL
treated with chemotherapy.3 Other definitions of bulky disease associated with poor
outcome in stage II to IV NHL include a large mediastinal mass (greater than one-third
of chest diameter), a palpable abdominal mass, and a combination of para-aortic and
pelvic node involvement.3,4,7,13,16,17,23,26
D. Anatomic Sites
The anatomic sites that constitute the major structures of the lymphatic system include
groups and chains of lymph nodes, the spleen, the thymus, Waldeyer’s ring (a circular
band of lymphoid tissue that surrounds the oropharynx consisting of the palatine,
lingual, and pharyngeal tonsils), the vermiform appendix, and the Peyer’s patches of
the ileum. Minor sites of lymphoid tissue include the bone marrow, liver, skin, lung,
pleura, and gonads. Involvement of extranodal sites is more common in NHL than in
Hodgkin lymphoma.
E. Histologic Type
The protocol recommends the World Health Organization (WHO) Classification of Lymphoid Neoplasms, which is shown below.27,28 This classification encompasses both nodal and extranodal lymphomas and outlines the immunobiologic features of the defined entities that aid in the diagnosis. The prognostic information necessary to determine treatment of lymphoma is, in general, provided by the histologic type.
WHO Classification of Lymphoid Neoplasms

B-cell Neoplasms
Precursor B-cell neoplasms
Precursor B-lymphoblastic lymphoma/leukemia Chronic lymphocytic leukemia/small lymphocytic lymphoma Lymphoplasmacytic lymphoma / Waldenström macroglobulinemia Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid Grade 1: 0 to 5 centroblasts per high power field# Grade 2: 6 to 15 centroblasts per high power field# Grade 3: greater than 15 centroblasts per high power field# Non-Hodgkin Lymphoma • Hematologic System
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Grade 3b: centroblasts form solid sheets with no residual Follicular and diffuse: 25% to 75% follicular Focally follicular: less than 25% follicular Grade 1: 0 to 5 centroblasts per high power field# Grade 2: 6 to 15 centroblasts per high power field# Variants: Blastoid (classic or pleomorphic), others Burkitt lymphoma with plasmacytoid differentiation B-cell proliferations of uncertain malignant potential Post-transplant lymphoproliferative disorder, polymorphic # WHO guideline27 for high powered field (HPF) = high powered field of 0.159mm2 (40X objective, 18mm field of view ocular; count 10 HPF and divide by 10). If using a 10mm field of view ocular, count 8 HPF and divide by 10, or count 10 HPF and divide by 12 to get the number of centroblasts/0.159mm2 HPF. If using a 22-mm field of view ocular, count 7 HPF and divide by 10, or count 10 HPF and divide by 15 to get the number of centroblasts/0.159mm2 HPF. T-cell Neoplasms Precursor T-cell neoplasms Precursor T lymphoblastic lymphoma/leukemia Variants: small cell, cerebriform cell (Sézary cell-like) For Information Only
Hematologic System • Non-Hodgkin Lymphoma
Extranodal NK/T-cell lymphoma, nasal type Variants: gamma-delta T-cell lymphoma in other anatomic sites Subcutaneous panniculitic-like T-cell lymphoma Mycosis fungoides (MF) and Sézary syndrome Primary cutaneous anaplastic large cell lymphoma (C-ALCL) T-cell proliferation of uncertain malignant potential
Immunophenotypes and Genetics26-29
Precursor B lymphoblastic leukemia/lymphoma: Slg-, cytoplasmic µ chain 30%, CD19+,
CD20-/+, CD22+, CD79a+, TdT+, HLA-DR+, CD10+/-, CD34+/-,
CD13-/+, CD33-/+, IgH gene rearrangement +/-, IgL gene rearrangement -/+, TCR gene
rearrangement -/+, variable cytogenetic abnormalities

B-cell chronic lymphocytic leukemia (B-CLL): Faint SIgM+, SIgD+/-, CIg-/+, panB+
(CD19+, CD20+), CD5+, CD10-, CD23+, CD43+, CD11c-/+; IgH and IgL gene
rearrangements; trisomy 12-/+; 13q abnormalities-/+
Lymphoplasmacytic lymphoma: SIgM+, SIgD-/+, CIg+, PanB+, CD5-, CD10-, CD43+/-,
CD25-/+; IgH and IgL gene rearrangements
Splenic marginal zone lymphoma: SIgM+, SIgD+, CD20+, CD79a+, CD5-, CD10-,
CD23-, CD43-, nuclear cyclin D1-, CD103-, allelic loss at 7q21-32 (40% of cases)
Hairy cell leukemia: SIg+ (IgM, IgD, IgG, or IgA), PanB+, CD79a+, CD79b-, DBA.44+,
CD5-, CD10-, CD23-, CD11c+, CD25+, FMC7+, CD103+ (mucosal lymphocyte antigen
as detected by B-ly7), tartrate resistant acid phosphatase (TRAP)+; IgH and IgL gene
rearrangements
Plasma cell myeloma: CIg+ (IgG, IgA, rare IgD, IgM, or IgE or light chain only), PanB-,
(CD19-, CD20-, CD22-), CD79a+/-, CD45-/+, HLA-DR-/+, CD38+, CD56+/-, EMA-/+,
CD43+/-; IgH and IgL gene rearrangements; deletions most commonly 13q, and
occasional translocations, in particular t(11;14)(q13;q32)
Non-Hodgkin Lymphoma • Hematologic System
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Extranodal marginal zone B-cell lymphoma of MALT ( MALT lymphoma): SIg+ (IgM or IgA or IgG), SIgD-, CIg-/+, PanB+, CD5-, CD10-, CD23-, CD43-/+; IgH and IgL gene rearrangements, bcl-1 and bcl-2 germline, trisomy 3 or t(11;18)(q21;q21) may be seen Nodal marginal zone B-cell lymphoma : SIgM+, SIgD-, CIg-/+, PanB+, CD5-, CD10-, CD23-, CD43-/+; IgH and IgL gene rearrangements, bcl-1 and bcl-2 germline Follicular lymphoma: SIg+ (usually IgM +/- IgD, IgG, IgA), PanB+, CD10+/-, CD5-, CD23-/+, CD43-, CD11c-, CD25-; overexpression of BCL-2+ (useful to distinguish from reactive follicles); BCL6+ IgH and IgL gene rearrangements, t(14;18) with rearranged BCL-2 gene in 70-95% of cases Mantle cell lymphoma: SIgM+, SIgD+, lambda>kappa, PanB+, CD5+, CD10-/+, CD23-, CD43+, CD11c-, CD25-; IgH and IgL gene rearrangements, t(11;14); bcl-1 gene rearrangements (CCND1/cyclinD1/PRAD1) common Diffuse large B-cell lymphoma: SIg+/-, CIg-/+, PanB+, CD45+/-, CD5-/+, CD10-/+ (weak); IgH and IgL gene rearrangements; bcl-2 gene rearranged in 30% of cases, bcl-6/LAZ3 gene (chromosome 3q27) rearranged in 30% of cases, c-myc gene rearrangement uncommon Mediastinal (thymic) large B-cell lymphoma: SIg-/+, PanB+, (especially CD20, CD79a), CD45+/-, CD15-, CD30-/+ (weak); IgH and IgL gene rearrangements Burkitt lymphoma: SIgM+, PanB+, CD5-, CD10+, CD23-; IgH and IgL gene rearrangements, t(8;14) and variants t(2;8) and t(8;22); rearranged c-myc gene. EBV common (95%) in endemic cases and infrequent (15-20%) in sporadic cases, intermediate incidence (30-40%) in HIV-positive cases Atypical Burkitt/ Burkitt-like lymphoma: SIg+/- (IgM or IgG), CIg-/+, PanB+, CD5-, CD10-/+; IgH and IgL gene rearrangements, infrequent rearrangement of c-myc gene, bcl-2 gene rearranged in 30% of cases Precursor T-lymphoblastic lymphoma/leukemia: TdT+, CD7+, CD3+/-, variable expression of other PanT antigens, CD1a+/-, often CD4 and CD8 double positive or negative, Ig-, PanB-; variable rearrangement of TCR genes; IgH gene rearrangement -/+, most common chromosomal abnormalities involve 14q11-14 or 7q35; variable cytogenetic abnormalities reported T-cell prolymphocytic leukemia: TdT-, PanT+, (CD2, CD3, CD5, CD7) CD25-, CD4+/CD8->CD4+/CD8+>CD4-/CD8-; TCR gene rearrangements, 75% of cases show inv 14(q11;q32) T-cell large granular lymphocytic leukemia, T-cell type: TdT-, PanT+ (CD2, CD3+, CD5+/-, CD7-), TCR+, CD4-, CD8+, CD16+, CD56-, CD57+, CD25-; most cases show clonal rearrangements of TCR genes T- cell large granular lymphocytic leukemia, NK-cell type: TdT-, CD2+, CD3-, TCR-, CD4-, CD8+/-, CD16+/-, CD56+/-, CD57+/-, CD25-; TCR and Ig genes are germline For Information Only
Hematologic System • Non-Hodgkin Lymphoma
Adult T-cell lymphoma/leukemia (HTLV1+): TdT-, PanT+ (CD2+, CD3+, CD5+, CD7-)
CD4+, CD8-, CD25+; TCR gene rearrangements, clonally integrated HTLV1
Extranodal NK/T-cell lymphoma, nasal type: TdT-, CD2+, CD5-/+, CD7-/+, CD3-/+, may
be CD4+ or CD8+, CD56+/-; usually no rearranged TCR or Ig genes; often EBV
positive
Enteropathy-type T-cell lymphoma: TdT-, CD3+, CD7+, CD4-, CD8+/-, CD103+
(mucosal lymphocyte antigen, such as detection by HML-1) (see gastrointestinal
lymphoma protocol)
Hepatosplenic T-cell lymphoma : CD2+, CD3+, TCR gamma-delta+, TCRab-, CD5-,
CD7+, CD4-, CD8-/+, CD56+/-, CD25-; TCR- gene rearrangements, variable TCR-
gene rearrangements
Mycosis fungoides/Sézary syndrome: TdT-, PanT+ (CD2+, CD3+, CD5+, CD7-/+), most
cases CD4+/CD8-, CD25-/+; TCR gene rearrangements
Angioimmunoblastic T-cell lymphoma: TdT-, PanT+ (often with variable loss of some
PanT antigens), usually CD4+; TCR gene rearrangements in 75%; IgH gene
rearrangements in 10%, EBV often positive, but usually only in isolated neoplastic or
reactive cells

Peripheral T-cell lymphomas, unspecified: TdT-, PanT variable (CD2+/-, CD3+/-,
CD5+/-, CD7-/+), most cases CD4+, some cases CD8+, CD4-/CD8-, or CD4+/CD8+;
TCR gene rearrangements usual
Anaplastic large cell lymphoma: TdT-, CD30+, EMA+/-, PanT-/+, CD45+/-, CD25+/-,
CD15-/+, CD68-, lysozyme-, BNH9+/-; primary cutaneous form is EMA- and cutaneous
lymphocyte antigen+; TCR gene rearrangements > germline, 12-50% of adult cases
show t(2;5) resulting in a fusion on NPM gene (5q35) with ALK gene (2q23)
F. Special Studies: Specimen Handling
Specimens for the diagnosis of lymphoma require special handling in order to optimize
the histologic diagnosis and to prepare the tissue for performance of molecular and
other special studies. The guidelines detailed below are suggested for specimen
handling in cases of suspected lymphoma.
• Tissue should be received fresh. Unsectioned lymph nodes should not be immersed
• The fresh specimen size, color and consistency should be recorded, as should the presence or absence of any visible nodularity, hemorrhage, or necrosis after serial sectioning at 2-mm intervals perpendicular to the long axis of a lymph node. • Touch imprints may be made from the freshly cut surface, and the imprints fixed in • For cytogenetic studies or culture of microorganisms: submit a portion of the node • Fixation (record fixative[s] used for individual slices of the specimen): • B5 produces superior cytologic detail but is not suitable for DNA extraction and may impair some immunostains (eg, CD30). Non-Hodgkin Lymphoma • Hematologic System
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• Over-fixation (ie, more than 24 hours in formalin, more than 4 hours in B5) • Snap-frozen tissue is optimal for some immunostains and for DNA and RNA extractions. • Cover tissue samples (cut to approximately 1x1x0.3 cm) in OCT. • Immerse in dry ice/isopentane slush or liquid nitrogen.
G. Stage
In general, the TNM classification has not been used for staging of lymphomas
because the site of origin of the tumor is often unclear and there is no way to
differentiate among T, N, and M. Thus, a special staging system (Ann Arbor System) is
used for both Hodgkin lymphoma and NHL. The Ann Arbor classification for lymphomas
has been applied to NHL by the American Joint Committee (AJCC) on Cancer and the
International Union Against Cancer (UICC) (see below).30,31 For multiple myeloma, the
Durie-Salmon staging system is recommended by the AJCC. Both staging systems are
shown below.
Pathologic staging depends on biopsy or resection of one or more regional lymph
nodes, splenectomy, wedge liver biopsy, bone marrow biopsy, and biopsy of multiple
lymph nodes on both sides of the diaphragm to assess distribution of disease. Clinical
staging generally involves a combination of clinical, radiologic, and surgical procedures
and includes medical history, physical examination, laboratory tests (eg, complete
blood examination, and blood chemistry studies), imaging studies (eg, computed
tomography [CAT] scans, magnetic resonance imaging [MRI] studies, and nuclear
medicine studies), biopsy to determine diagnosis, extent of disease, and histologic type
of tumor (initial diagnosis is almost always made on biopsy), and often bone marrow
biopsy. Most commonly, staging of NHL is clinical rather than pathologic.
There is almost universal agreement that the stage of NHL is prognostically
significant.1-3,6,8,13,17,21
AJCC/UICC Staging for Non-Hodgkin Lymphomas30,31
Stage I
Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE)#, ## Involvement of 2 or more lymph node regions on the same side of the diaphragm (II), or localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE) ##,### Involvement of lymph node regions on both sides of the diaphragm (III), which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of the spleen (IIIS) or both (IIIE+S) ##,###, ^ Diffuse or disseminated involvement of 1 or more extralymphatic organs, with or without associated lymph node involvement; or isolated extralymphatic organ involvement in the absence of adjacent regional lymph node involvement, but in conjunction with disease in distant For Information Only
Hematologic System • Non-Hodgkin Lymphoma
site(s). Any involvement of the liver or bone marrow, or nodular involvement of the lung(s). ##,###,^ # Multifocal involvement of a single extralymphatic organ is classified as stage IE and not stage IV. ## For all stages, tumor bulk greater than 10 to 15 cm is an unfavorable prognostic factor.3 ### The number of lymph node regions involved may be indicated by a subscript: eg, II3. For stages II to IV, involvement of more than 2 sites is an unfavorable prognostic factor.3 ^ For stages III to IV, a large mediastinal mass is an unfavorable prognostic factor.3 AJCC/UICC Staging for Plasma Cell Myeloma30,31
Stage I
Normal bone x-rays or a solitary bone lesion One or more of the following are included: Disease fitting neither stage I nor stage III
Note: Patients are further classified as (A) serum creatinine less than 2.0 mg/dL, or
(B) serum creatinine 2.0 mg/dL or greater. The median survival for stage IA disease is
about 5 years, and that for stage IIIB disease is 15 months.30
H. Direct Spread into Adjacent Tissues or Organs
Direct spread of a lymphoma into adjacent tissues or organs does not influence
classification of stage.
References
1. Shipp MA, Harrington DP, Anderson JR, et al. A predictive model for aggressive
non-Hodgkin lymphoma. N Engl J Med. 1993;329:987-994. 2. Shipp MA. Prognostic factors in aggressive non-Hodgkin lymphoma. Blood. 3. Crump M, Gospodarowicz MK. Non-Hodgkin malignant lymphoma. In: Gospodarowicz MK, Henson DE, Hutter RVP, O’Sullivan B, Sobin LH, Wittekind C, eds. Prognostic Factors in Cancer. New York, NY: Wiley-Liss; 2001:689-703. Non-Hodgkin Lymphoma • Hematologic System
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