Non-Hodgkin’s Lymphoma

Protocol applies to non-Hodgkin’s lymphoma involving any organ system except the gastrointestinal tract.

Procedures

•  Cytology

•  Incisional Biopsy

•  Resection of Lymph Node or Other Organ

 

This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.

 

It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with the document. Where a physician chooses to deviate from the protocol based on the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.

 

The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.

 

I. Cytologic material            back     Top     Main Page

 

      A.  CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Patient identification number

c.   Age (birth date) (Note A)

d.   Gender (Note B)

2.   Responsible physician(s)

            3.   Date of procedure

4.   Other clinical information

a.   Relevant history (e.g. duration of lymphadenopathy or other mass; previous diagnosis and treatment for lymphoma, Hodgkin’s disease or other malignancy; immunosuppression; AIDS)

b.   Relevant findings (e.g. distribution of lymphadenopathy; signs and symptoms; imaging studies; serum LDH level) (Note C)

c.   Clinical diagnosis

d.   Clinical stage, if known

e.   Specific procedure (FNA, tap of effusion, other)

f.    Operative findings

g.   Anatomic site(s) of specimen(s) (Note D)

 

 

      B.   MACROSCOPIC EXAMINATION

1.   Specimen

a.   Unfixed/fixed (specify fixative)

b.   Number of slides received, if appropriate

c.   Quantity and appearance of fluid specimen, if appropriate

d.   Other (e.g. cytologic preparation from tissue)

e.   Results of intraprocedural consultation

2.   Material submitted for microscopic evaluation (e.g. FNA, cytospin of fluid, other)

3.   Special studies, specify (e.g. flow cytometry for immunophenotyping, cytochemistry, immunocytochemistry, 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 (e.g. 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

 

 

II.  Incisional biopsy            back     Top     Main Page

 

      A.  CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Patient identification number

c.   Age (birth date) (Note A)

d.   Gender (Note B)

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history (e.g. duration of lymphadenopathy or other mass; previous diagnosis and treatment for lymphoma, Hodgkin’s disease or other malignancy; immunosuppression; AIDS)

b.   Relevant findings (e.g. distribution of lymphadenopathy; signs and symptoms; imaging studies; serum LDH level) (Note C)

c.   Clinical diagnosis

d.   Clinical stage, if known

e.   Specific procedure (e.g. lymph node biopsy, liver biopsy)

f.    Operative findings

g.   Anatomic site(s) of specimen(s) (Note D)

 

 

      B.   MACROSCOPIC EXAMINATION

1.   Specimen

a.   Unfixed/fixed (specify fixative)

      [Note: Fresh frozen tissue should be saved, if possible, for immuno-phenotyping 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 (e.g. flow cytometry for immunophenotyping, histochemistry,  immunohistochemistry, cytogenetic analysis)

 

      C.  MICROSCOPIC EVALUATION

1.   Tumor

a.   Histologic type (Note E)

b.   Other characteristics (e.g. 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                  back     Top     Main Page

 

      A.  CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Patient identification number

c.   Age (birth date) (Note A)

d.   Gender (Note B)

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history (e.g. duration of lymphadenopathy or other mass; previous diagnosis and treatment for lymphoma, Hodgkin’s disease or other malignancy; immunosuppression; AIDS)

b.   Relevant findings (e.g. distribution of lymphadenopathy; signs and symptoms; imaging  studies; serum LDH level) (Note C)

c.   Clinical diagnosis

d.   Clinical stage, if known

e.   Specific procedure (e.g. lymph node excision, splenectomy, other)

f.    Operative findings

g.   Anatomic site(s) of specimen(s) (Note D)

 

 

      B.   MACROSCOPIC EXAMINATION

1.   Specimen

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

2.   Tumor

a.   Number of lesions (Note F)

b.   Location (Note F)

c.   Configuration

d.   Dimensions

e.   Descriptive characteristics (e.g. color/consistency)

f.    Direct extension to other organ(s) or structure(s) (Note G)

g.   Noncontiguous tumor involvement of other organ(s) or structure(s) (Note F)

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 (e.g. flow cytometry for immunophenotyping, histochemistry, immunohistochemistry, cytogenetic analysis)

 

 

      C.  MICROSCOPIC EVALUATION

1.   Tumor

a.   Histologic type (Note E)

b.   Direct extension to other organ(s) or structure(s)

2.   Additional pathologic findings, if present (e.g. reactive follicular hyperplasia)

3.   Other tissues submitted (if distant involvement by lymphoma: specify site) (Note F)

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       back     Top     Main Page

Age is a risk factor independently associated with survival in non-Hodgkin’s 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 (i.e., stage I and II, see below), older patients are at greater risk for relapse than younger patients.(3,6-16)

 

B.  Gender       back     Top     Main Page

Across all grades and stages of NHL, male gender 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            back     Top     Main Page

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 (>38.5oC), unexplained weight loss (>10% body weight) in the 6 months before diagnosis, and drenching night sweats are used to define two categories for each stage of NHL: i.e., A (symptoms absent) and B (symptoms present). The presence of B symptoms are known to correlate with extent of disease (stage and tumor bulk), but they 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 (i.e., 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) Tumor greater than 5-10 cm in diameter is associated with higher rates of relapse of stage I and II NHL treated with radiotherapy.(13) 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-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       back     Top     Main Page

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’s disease.

 

E.  Histologic Type       back     Top     Main Page

The protocol recommends the most recently proposed lymphoma classification of the International Lymphoma Study Group (i.e. the Revised European-American Lymphoma Classification) shown below. This classification encompasses both nodal and extranodal lymphomas and outlines the immunobiologic features of the defined entities that aid in the diagnosis.(26,27) The prognostic information necessary to determine treatment of lymphoma is, in general, provided by the histologic type.

 

Revised European-American Lymphoma Classification (REAL Classification)

B Cell Neoplasms

•      Precursor B-lymphoblastic lymphoma/leukemia

•      B-cell chronic lymphocytic leukemia/prolymphocytic leukemia

•      Small lymphocytic lymphoma

•      Mantle cell lymphoma

•      Lymphoplasmacytic / Immunocytoma

•      Follicle center lymphoma

            Follicular    Grade I

            Follicular    Grade II

            Follicular    Grade III

•      Diffuse predominantly small cell (provisional)

•      Extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of MALT type)

•      Nodal marginal zone B-cell lymphoma (monocytoid B-cell lymphoma) (provisional)

•      Splenic marginal zone B-cell lymphoma (provisional)

•      Hairy cell leukemia

•      Plasmacytoma/plasma cell myeloma

•      Diffuse large B-cell lymphoma

•      Primary mediastinal B-cell lymphoma

•      Burkitt’s lymphoma

•      High grade B-cell lymphoma, Burkitt-like (provisional)

 

T-Cell Neoplasms

•      Precursor T-lymphoblastic lymphoma/leukemia

•      T-cell chronic lymphocytic leukemia/prolymphocytic leukemia

•      Large granular lymphocyte leukemia

        -   T-cell type

        -   NK cell type

•      Mycosis fungoides / Sézary’s syndrome

•      Peripheral T-cell lymphomas, unspecified (including provisional subtype: subcutaneous panniculitic T-cell lymphoma)

•      Hepatosplenic  T-cell lymphoma (provisional subtype of peripheral T-cell lymphoma)

•      Angioimmunoblastic T-cell lymphoma

•      Nasal/nasal type T/NK cell (angiocentric) lymphoma

•      Intestinal T-cell lymphoma (± gluten-sensitive enteropathy)

•      Adult T-cell lymphoma/leukemia

•      Anaplastic large cell lymphoma, T- and null-cell types

 

Other Classifications

Other current histologic classifications of NHL (Working Formulation, Kiel) used in the literature on lymphoma are shown below. The Kiel and Working Formulation establish prognostic categories or histologic grades as well.

 

Working Formulation of Non-Hodgkin’s Lymphoma

Low Grade*

Malignant lymphoma, small lymphocytic

        -   Consistent with chronic lymphocytic leukemia

        -   Plasmacytoid

Malignant lymphoma, follicular, predominantly small cleaved cell

Malignant lymphoma, follicular, mixed small cleaved and large cell

 

Intermediate Grade*

Malignant lymphoma, follicular, predominantly large cell

Malignant lymphoma, diffuse, small cleaved cell

Malignant lymphoma, diffuse, mixed small and large cell

Malignant lymphoma, diffuse, large cell

        -   Cleaved cell

        -   Noncleaved cell

 

High Grade*

Malignant lymphoma, large cell, immunoblastic

        -   Plasmacytoid

        -   Clear cell

        -   Polymorphous

Malignant lymphoma, lymphoblastic

        -   Convoluted

        -   Nonconvoluted

Malignant lymphoma, small noncleaved cell

        -   Burkitt’s

        -   Non-Burkitt’s

* Grade refers to clinical prognostic group.

 

Kiel Classification of Non-Hodgkin’s Lymphoma

Low Grade* B Cell

Lymphocytic:

Chronic lymphocytic leukemia

Prolymphocytic leukemia

Hairy cell leukemia

Lymphoplasmacytic (immunocytoma)   

Plasmacytic (plasmacytoma)

Centroblastic/centrocytic

Centrocytic (mantle cell)

Monocytoid B cell

 

High Grade*B Cell

Centroblastic
Immunoblastic

Anaplastic large cell

Burkitt’s lymphoma

Lymphoblastic

 

Low Grade* T Cell

Lymphocytic:

Chronic lymphocytic leukemia

Prolymphocytic leukemia

Small cerebriform cell (mycosis fungoides)

Lymphoepithelioid cell (Lennert’s)

Angioimmunoblastic

T-zone

Pleomorphic, small cell (HTLV +/-)

 

High Grade* T Cell

Pleomorphic, medium and large cell (HTLV +/-)

Immunoblastic (HTLV +/-)

Anaplastic large cell

Lymphoblastic

 

* Grade refers to histologic grade.

 

Immunophenotypes and Genetics (R.E.A.L. Classification)(26-27)

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)/prolymphocytic leukemia (B-PLL)/small lymphocytic lymphoma: (B-CLL) Faint SIgM+, SIgD+/-, CIg-/+, panB+, CD5+, CD10-, CD23+, CD43+, CD11c-/+, CD25-/+ (B-PLL) More likely strong SIg+, CD22+, and CD5-. All of above - IgH and IgL gene rearrangements; trisomy 12-/+; 13q abnormalities-/+

 

Lymphoplasmacytic lymphoma: SIgM+, SIgD-/+, CIg+, PanB+, CD5-, CD10-, CD43+/-, CD25-/+; IgH and IgL gene rearrangements

 

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

 

Follicular center lymphoma, follicular: SIg+ (usually IgM +/- IgD, IgG, IgA), PanB+, CD10+/-, CD5-, CD23-/+, CD43-, CD11c-, CD25-; overexpression of bcl-2 protein useful in distinction to reactive follicles; IgH and IgL gene rearrangements, t(14;18) with rearranged bcl-2 gene in 70-95% of cases

 

Extranodal marginal zone B-cell lymphoma (low-grade B-cell lymphoma of MALT type): 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 (provisional): SIgM+, SIgD-, CIg-/+, PanB+, CD5-, CD10-, CD23-, CD43-/+; IgH and IgL gene rearrangements, bcl-1 and bcl-2 germline

 

Splenic marginal zone B-cell lymphoma (provisional): CIgM+, CIgD-, CIg-/+, PanB+, CD5-, CD10-, CD23-, CD25-, IgH and IgL gene rearrangements

 

Hairy cell leukemia: SIg+ (IgM, IgD, IgG, or IgA), PanB+, DBA44+, CD11c++, CD25+, CD103+ (mucosal lymphocyte antigen as detected by B-ly7), tartrate-resistant acid phosphatase+; IgH and IgL gene rearrangements

 

Plasmacytoma/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 or deletions, occasional cases t(11;14)

 

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

 

Primary mediastinal large B-cell lymphoma: SIg-/+, PanB+, (especially CD20, CD79a), CD45+/-, CD15-, CD30-/+ (weak); IgH and IgL gene rearrangements

 

Burkitt’s 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

 

High grade B-cell lymphoma, Burkitt-like (provisional): SIg+/- (IgM or IgG), CIg-/+, PanB+, CD5-, CD10-/+; IgH and IgL gene rearrangements, infrequent rearrangment 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 CLL/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)

 

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

 

Large granular lymphocytic leukemia, NK cell type: TdT-, CD2+, CD3-, TCR-, CD4-, CD8+/-, CD16+/-, CD56+/-, CD57+/-, CD25-; TCR and Ig genes are germline

 

Mycosis fungoides/Sézary syndrome: TdT-, PanT+ (CD2+, CD3+, CD5+, CD7-/+), most cases CD4+/CD8-, CD25-/+; TCR gene rearrangements

 

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

 

Hepatosplenic g-d T-cell lymphoma (provisional): CD2+, CD3+, TCRgd+, TCRab-, CD5-, CD7+, CD4-, CD8-/+, CD56+/-, CD25-; TCR- gene rearrangements, variable 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

 

Nasal/nasal type T/NK cell (angiocentric) lymphoma: TdT-, CD2+, CD5-/+, CD7-/+, CD3-/+, may be CD4+ or CD8+, CD56+/-; usually no rearranged TCR or Ig genes; often EBV positive

 

Intestinal T-cell lymphoma: TdT-, CD3+, CD7+, CD4-, CD8+/-, CD103+ (mucosal lymphocyte antigen, such as detection by HML-1) (see gastrointestinal lymphoma protocol)

 

Adult T-cell lymphoma/leukemia: TdT-, PanT+ (CD2+, CD3+, CD5+, CD7-) CD4+, CD8-, CD25+; TCR gene rearrangements, clonally integrated HTLV1

 

Anaplastic large cell lymphoma, T- and null-cell types: 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.  Stage          back     Top     Main Page

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’s disease 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).(28)

 

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 (e.g. complete blood examination, and blood chemistry studies), imaging studies (e.g. CAT scans, MRI studies, and nuclear medicine studies), biopsy to determine diagnosis 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’s Lymphomas (28)

Stage I       Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE)*,**

Stage II      Involvement of two or more lymph node regions on the same side of the diaphragm (II), or localized involvement of a single associated extralymphatic organ or site and its regional lymph nodes with or without other lymph node regions on the same side of the diaphragm (IIE)**,***

Stage III     Involvement of lymph node regions on both sides of the diaphragm (III) that may  be accompanied by localized involvement of an extralymphatic
organ or site (IIIE), by involvement of the spleen (IIIS) or both (IIIE+S)**,***,****

Stage IV     Disseminated (multifocal) involvement of one or more extralymphatic organs with or without associated lymph
node involvement, or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement**,***,****

 

* Multifocal involvement of a single extralymphatic organ is classified as stage IE and not stage IV.

 

** For all stages, tumor bulk >10-15 cm is an unfavorable prognostic factor.(3)

*** The number of lymph node regions involved may be indicated by a subscript: e.g. II3. For stages II-IV, involvement of more than two sites is an unfavorable prognostic factor.(3)

 

**** For stages III-IV, a large mediastinal mass is an unfavorable prognostic factor.(3)

 

G.  Direct Spread into Adjacent Tissues Or Organs                   back     Top     Main Page

Direct spread of a lymphoma into adjacent tissues or organs does not influence classification of stage.

 

 

REFERENCES                        back     Top     Main Page

 1.    Shipp MA, Harrington DP, Anderson JR, et al. A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993;329:987-994.

 2.    Shipp MA. Prognostic factors in aggressive non-Hodgkin’s lymphoma. Blood. 1994;83:1165-1173.

 3.    Gospodarowicz MK, Hayat M. Non-Hodgkin’s Lymphomas in Prognostic Factors in Cancer. Hermanek P, Gospodarowicz MK, Henson DE, Hutter RVP, Sobin LH, eds. Berlin-New York, Springer-Verlag, 1995.

 4.    Gospodarowicz MK, Bush RS, Brown TC, et al. Prognostic factors in nodular lymphomas: a multivariate analysis based on the Princess Margaret experience. Int J Radiat Oncol Biol Phys. 1984;10:489-497.

 5.    Dana BW, Dahlberg S, Nathwani BN, et al. Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy. J Clin Oncol. 1993;11:644-651.

 6.    Hayward RL, Leonard RC, Prescott RJ, et al. A critical analysis of prognostic factors for survival in intermediate and high grade non-Hodgkin’s lymphoma. Scotland and Newcastle Lymphoma Group Therapy Working Party. Br J Cancer. 1991;63:945-952.

 7.    Kaminski MS, Coleman CN, Colby TV, et al. Factors predicting survival in adults with stage I and II large-cell lymphoma treated with primary radiation therapy. Ann Intern Med. 1986;104:747-56.

 8.    Lindh J, Lenner P, Osterman B, et al. Prognostic significance of serum lactic dehydrogenase levels and fraction of S-phase cells in non-Hodgkin’s lymphomas. Eur J Hematol. 1993;50:258-263.

 9.    O’Reilly SE, Hoskins P, Klimo P, et al. MACOP-B and VACOP-B in diffuse large lymphomas and MOPP/ABV in Hodgkin’s disease. Ann Oncol. 1991;1:17-23.

10.   Shimoyama M, Ota K, Kitutchi M, et al. Major prognostic factors of adult factors of adult patients with advanced B-cell lymphoma treated with vincristine, cyclophosphamide, prednisone and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M). Jpn J Clin Oncol. 1988:18;113-124.

11.   Soubeyran P, Eghbali H, Bonichon, et al. Localized follicular lymphomas: prognosis and survival of stage I and II in a retrospective series of 103 patients. Radiother Oncol. 1988;13:91-98.

12.   Stein RS, Greer JP, Cousar JB, et al. Malignant lymphomas of follicular centre cell origin in man. VII. Prognostic features in small cleaved lymphoma. Hematol Oncol. 1989;7:381-391.

13.   Sutcliffe SB, Gospodarowicz MK, Bush RS, et al. Role of radiation therapy in localized non-Hodgkin’s lymphoma. Radiother Oncol. 1985;4:211-223.

14.   Taylor RE, Allan SG, McIntyre MA, et al. Low grade stage I and II non-Hodgkin’s lymphoma: results of treatment and relapse pattern following therapy. Clin Radiol. 1988;39:287-290.

15.   Velasquez WS, Fuller LM, Jagannath S, et al. Stages I and II diffuse large cell lymphomas: prognostic factors and long-term results with CHOP-bleo and radiotherapy. Blood. 1991;77:942-947.

16.   Velasquez WS, Jagannath S, Tucker TS, et al. Risk classification as the basis for clinical staging of diffuse large-cell lymphoma derived from 10-year survival data. Blood. 1989;74:551-557.

17.   Steward WP, Crowther D, McWilliam LJ, et al. Maintenance chlorambucil after CVP in the management of advanced stage, low grade histologic type non-Hodgkin’s lymphoma. A randomized prospective study with assessment of prognostic factors. Cancer. 1988;61:441-447.

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Authors

Carolyn Compton, MD, PhD; Nancy L. Harris, MD; and Dennis W. Ross, MD, PhD

 

©1999. College of American Pathologists (CAP). All rights reserved. None of the contents of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without prior written permission of the publisher.

 

Contributors:                back     Top     Main Page

      CAP Cancer Committee; Annik van den Abbeele, MD; Judith Ferry, MD; Claire Fung, MD; Irene Kuter, MD; Peter Mauch, MD