Hodgkin’s Disease

Protocol applies to Hodgkin’s disease involving any organ system except the gastrointestinal tract.

Procedures

•  Cytology

•  Incisional Biopsy

•  Excisional Biopsy

•  Staging Laparotomy

 

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

2.   Responsible physician(s)

3.   Date of procedure

4.   Other cinical information

      a.   Relevant history

      (1) previous diagnosis and treament for lymphoma

      (2) previous or current Epstein-Barr virus infection

b.   Relevant findings (e.g. distribution of lymphadenopathy, signs, symptoms; imaging studies) (Note B)

c.   Clinical diagnosis

d.   Procedure (e.g. FNA, other)

e.   Anatomic site(s) of specimen(s) (Note C)

                                                                 

 

      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, cell block)

3.   Special studies (specify) (e.g. flow cytometry for immunophenotyping, cytochemistry, immunocytochemistry, cytogenetic analysis) (Note D)

 

      C.  MICROSCOPIC EVALUATION

1.   Adequacy of specimen (if unsatisfactory for evaluation, specify reason)

2.   Tumor, if present

a.   Histologic type, if possible (Note E)

b.   Other characteristics (e.g. necrosis; types of non-neoplastic background cells present)

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 clinical information, as appropriate

c.   Correlation with other specimens, 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)

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history

(1)  previous diagnosis and treament for lymphoma

(2)  previous or current Epstein-Barr virus infection

b.   Relevant findings (e.g. distribution of lymphadenopathy, signs, symptoms; imaging studies) (Note B)

c.   Clinical diagnosis

d.   Procedure

e.   Anatomic site(s) of specimen(s) (Note C)

 

 

      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] (Note D)

b.   Number of pieces

c.   Largest dimension of each piece

d.   Results of intraoperative consultation

2.   Submit all nonfrozen tissue for microscopic evaluation and special studies

3.   Special studies (specify) (e.g. flow cytometry for immunophenotyping, histochemistry, immunohistochemistry, cytogenetic analysis) (Note D)

 

C.  MICROSCOPIC EVALUATION

      1.   Tumor

            a.   Histologic type (Note E)

b.   Histologic grade, if applicable (Note F)

      2.   Additional pathologic findings, if present (Note G)

      3.   Results/status of special studies (specify)

      4.   Comments

a.   Correlation with intraoperative consultation, as appropriate

b.   Correlation with other specimens, as appropriate

c.   Correlation with clinical information, as appropriate

 

III.  Excisional biopsy         back     Top     Main Page

 

      A.  CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Patient identification

c.   Age (birth date) (Note A)

d.   Gender

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history

(1)  previous diagnosis and treament for lymphoma

(2)  previous or current Epstein-Barr virus infection

b.   Relevant findings (e.g.distribution of lymphadenopathy, signs, symptoms; imaging studies) (Note B)

c.   Clinical diagnosis

d.   Procedure (e.g. axillary lymph node excision)

e.   Operative findings

f.    Anatomic site(s) of specimen(s) (Note C)

 

 

      B.   MACROSCOPIC EXAMINATION

1.   Specimen

a.   Organ(s)/tissue(s) (specify)

b.   Unfixed/fixed (specify fixative)

      [Note: Fresh frozen tissue should be saved, if possible, for immunophenotyping and molecular genetic studies] (Note D)

c.   Number of pieces

d.   Dimensions

e.   Results of intraoperative consultation

2.   Tumor

a.   Dimensions

b.   Configuration

c.   Descriptive characteristics (e.g. color, consistency)

3.   Additional pathologic findings, if present

4.   Tissues submitted for microscopic evaluation

a.   Tumor, submit all

b.   Other lesions

c.   Section(s) of tissue uninvolved by tumor

d.   Frozen section tissue fragment(s) (unless saved for special studies)

e.   Other tissue(s)/organ(s)

5.   Special studies (specify) (e.g. flow cytometry for immunophenotyping, histochemistry, immunohistochemistry, cytogenetic analysis) (Note D)

 

 

      C.  MICROSCOPIC EVALUATION

1.   Tumor

a.   Histologic type (Note E)

b.   Histologic grade (if applicable) (Note F)

2.   Other organs or tissues

c.   If distant involvement by tumor: specify site (Note H)

d.   Specify if direct extension of tumor into other organ or tissue (Note I)

3.   Additional pathologic findings, if present (Note G)

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

 

IV.  Staging laparotomy (Note J)                      back     Top     Main Page

 

 

      A.  CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Patient identification number

c.   Age (birth date) (Note A)

d.   Gender

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history

(1)  previous diagnosis and treament for lymphoma

(2)  previous or current Epstein-Barr virus infection

b.   Relevant findings (e.g. distribution of lymphadenopathy, signs, symptoms; imaging studies) (Note B)

c.   Clinical diagnosis

d.   Procedure (e.g. staging laparotomy)

e.   Operative findings

f.    Anatomic site(s) of specimen(s) (Note C)

 

 

      B.   MACROSCOPIC EXAMINATION

1.   Specimens

a.   Organ(s)/tissue(s) included

b.   Fixed/unfixed (specify fixative)

c.   Number of pieces

d.   Dimensions; weight (spleen)

e.   Orientation of specimens (if indicated by surgeon)

f.    Results of intraoperative consultation(s)

2.   Spleen

a.   Weight (Note: slice at 1 cm intervals and fix 6-12 hr; then slice at 5 mm intervals)

b.   Lesions

(1)  Number (count individual lesions up to to 10; if more, state “>10”)

(2)  Size range

(3)  Location

(4)  Configuration

(5)  Descriptive characteristics (e.g. color, consistency)

(6)  Direct extension to other organ(s) or structure(s) (Note I)

c.   Additional pathologic findings, if present

3.   Lymph nodes

a.   Number of lesions, if discernible

b.   Descriptive characteristics (e.g. color, consistency)

c.   Additional pathologic findings, if present

4.   Bone marrow biopsy

a.   Size

b.   Descriptive characteristics (e.g. color, consistency)

5.   Other organ(s) or structure(s)

a.   Size

b.   Descriptive characteristics (e.g. color, consistency)

c.   Noncontiguous lesions, if discernible (Note H)

(1)  number

(2)  size

(3)  descriptive characteristics

d.   Additional pathologic findings, if present

6.   Tissues submitted for microscopic evaluation

a.   Lymph nodes, liver biopsy, bone marrow biopsy: submit entirely

b.   Spleen:

(1)  nodules present: section of each nodule up to 6

(2)  no nodules present: 6 random sections

c.   Section of tissue uninvolved by tumor

d.   Other separately submitted lesions/nodules

e.   Frozen section tissue fragment(s) (unless saved for special studies)

f.    Other tissue(s)/organ(s)

7.   Special studies (specify) (e.g. flow cytometry for immunophenotyping, histochemistry, immunohistochemistry, cytogenetic analysis)

 

 

      C.  MICROSCOPIC EVALUATION

1.   Tumor

a.   Histologic type (Note E)

b.   Histologic grade, if appropriate (Note F)

c.   Extent of involvement (Note J)

d.   Direct extension to other organ(s) or structure(s) (Note I)

 

2.   Other tissues submitted (specify)

a.   If distant involvement by lymphoma: specify site (Note J)

3.   Additional pathologic findings, if present (Note G)

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.  Age            back     Top     Main Page

In Hodgkin’s disease, patient age above 40 or 50 years has been shown to be associated with decreased survival compared to younger ages. Several multivariate analyses have shown that age has independent prognostic impact on cause-specific survival.(1-5)

 

B.  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 Hodgkin’s disease (across all stages).  Among these are systemic symptoms such as fever (>38.5oC), weight loss (>10% body weight), night sweats, large tumor burden (including tumor bulk and number of sites), and a large (>1/3 the width of the widest thoracic diameter) mediastinal mass.(1, 6-11)  These systemic symptoms are used to define two categories for each stage of Hodgkin’s disease: i.e. A (symptoms absent) and B (symptoms present).  The presence of B symptoms has been regarded as an important prognostic factor for survival in many studies, but multivariate analyses in studies with highly accurate evaluations of extent of disease have shown that B symptoms correlate with extent of disease but are not always of independent significance.(1,3,12-13)  However, fever and/or weight loss have been shown to be independently associated with decreased survival in patients with stage II Hodgkin’s disease.(14)

 

C.  Anatomic Sites        back     Top     Main Page

Stages of Hodgkin’s disease (see Note H) are classified by involvement of lymph node “regions,” rather than specific lymph nodes or specific lymph node groups (e.g. jugular, tracheal, etc). Single lymph node “regions” are defined as follows:(15)

      - Lymph nodes of head, neck, and face

      - Intrathoracic lymph nodes

      - Intra-abdominal lymph nodes

      - Lymph nodes of the axilla or arm

      - Lymph nodes of the inguinal region or leg

      - Pelvic lymph nodes

 

Involvement of a given region may include involvement of more than one lymph node or lymph node group.

 

D.  Special Studies       back     Top     Main Page

Cytogenetic studies, flow cytometry, and HLA typing are not uniformly useful as prognostic indicators in Hodgkin’s disease.(1,16)  However, special studies may be useful diagnostically. The main differential diagnosis in most cases of Hodgkin’s disease is non-Hodgkin’s lymphoma.  If necessary, immunohistochemical studies (immunophenotyping) and genetic studies (i.e. gene rearrangement) should be performed to confirm the diagnosis and exclude non-Hodgkin’s lymphoma.(17) The typical immunophenotypes and genetic alterations associated with the specific histologic types of Hodgkin’s disease are listed in Note E below.

 

E.  Histologic Type       back     Top     Main Page

Histologic classification of Hodgkin’s disease should be based on sections of paraffin-embedded tissue stained with hematoxylin and eosin.  Primary diagnosis of Hodgkin’s disease is rarely made by cytological analysis. However, cytologic examinations may be useful in diagnosing relapse in patients with a history of Hodgkin’s disease.

 

Hodgkin’s disease is traditionally categorized histologically by the Rye Classification, which defines four major histologic types. The Revised European American Lymphoma (REAL) Classification of the International Lymphoma Study Group recognizes the four traditional types but has included a provisional category that is histologically distinct: i.e. lymphocyte-rich classical Hodgkin’s disease. Both classifications are listed below.

 

Rye Classification of Hodgkin’s Disease

Lymphocyte predominance

Nodular sclerosis

Mixed cellularity

Lymphocyte depletion

 

REAL Classification of Hodgkin’s Disease

Lymphocyte predominance, nodular

Nodular sclerosis

Mixed cellularity

Lymphocyte depletion

Lymphocyte-rich, classical Hodgkin’s disease (provisional category)

 

In the current era of improved treatment with high rates of cure, the prognostic value of the histologic type of Hodgkin’s disease is limited. Formerly, mixed cellularity and lymphocyte depletion Hodgkin’s disease were associated with increased risk of death from disease compared to nodular sclerosis and lymphocyte predominance. Currently, histologic type is of independent prognostic value only in clinical stage I and II disease treated with radiation therapy alone.(1)

The immunophenotypic characteristics and the genetic alterations that typify each of the subtypes of Hodgkin’s disease of the REAL Classification are as follows:(18)

 

 Lymphocyte predominance, nodular: CD45+, PanB+, CDw75+,EMA+/-,CD15-,CD30-/+,J-chain+, usually Ig-, numerous CD57+ lymphocytes around lymphocytic and hystiocytic (L and H) cells; Ig and TCR genes germline, tumor cells usually EBV-

Nodular sclerosis: CD30+, CD15+, CD45- (may be CD45+ on frozen section), usually PanB- and PanT-, CD20-/+, EMA-; Ig and TCR genes usually germline, occasional IgH gene rearrangement, occasional bcl-2 gene rearrangement, EBV infection of tumor in 40 percent of cases

 

Mixed cellularity: CD30+, CD15+/-, CD45- (may be CD45+ on frozen sections), usually PanB- and
PanT-, CD20-/+, EMA-; Ig and TCR genes usually germline, EBV infection of tumor cells in 60-70 percent of cases

 

Lymphocyte depletion: CD30+, CD15+/-, CD45-, PanB-, PanT-, EMA-; Ig and TCR genes germline

 

Lymphocyte-rich classical Hodgkin’s disease (provisional entity): CD30+, CD15+/-, CD45- usually PanB- and PanT-, EMA-; Ig and TCR genes germline, EBV-/+

 

F.  Histologic Grade                 back     Top     Main Page

Histologic grading has been developed only for nodular sclerosis (NS) Hodgkin’s disease and is not applicable to other histologic types of Hodgkin’s disease.  Nodular sclerosis comprises 75% of all cases.  It does not coexist with or transform into other histologic types, but the individual nodules may show a variety of histologic appearances that range from a lymphocyte predominance to a lymphocyte depletion background with scant to plentiful neoplastic cells, respectively.  In a large series of pathologic stage I and II Hodgkin’s disease (see below) reported by the British National Lymphoma Investigation, patients with nodular sclerosis having either extensive and easily recognizable areas of lymphocyte depletion or numerous pleomorphic Hodgkin’s (Reed-Sternberg) cells had a decreased survival independent of disease stage.(19)  Thus, a two-tiered grading system for nodular sclerosis Hodgkin’s disease based on the proportion of lymphocyte depleted nodules present in histologically examined tissue has been proposed as follows:

Grade I (NSI):

1) <25% of nodules show lymphocyte depletion

or

2) <25% of nodules show numerous anaplastic

     Hodgkin’s cells without depletion of lymphocytes

 

Grade II (NSII):

1) >25% of nodules show lymphocyte depletion

or

2) >25% of nodules show numerous anaplastic

     Hodgkin’s cells without depletion of lymphocytes

 

Reported results from different centers differ as to the prognostic importance of grading, but overall, the most significant correlation appears to be that NSI is more indolent than NSII.  With optimal therapy, however, it appears that the difference in natural history can be overcome.(6)

 

G.  Other Pathologic Findings               back     Top     Main Page

Of particular importance are the distinctive pathologic findings that are known to be associated with Hodgkin’s disease.  Progressively transformed germinal centers (PTGC), for example, are an unusual type of reactive follicle that are often found at the periphery of a lymph node involved by nodular lymphocyte predominance Hodgkin’s disease or, less often, other types of Hodgkin’s disease. However, PTGC may also occur in settings unrelated to Hodgkin’s disease, such as reactive lymphoid hyperplasia. PTGC appear as germinal centers that are infiltrated and enlarged by small lymphocytes of the mantle zone type.(16) Other pathologic lesions that may be seen in association with Hodgkin’s disease and, therefore, should be specifically reported in patients in whom Hodgkin’s disease is suspected clinically include granulomatous inflammation and changes reminiscent of Castleman’s disease (hyaline-vascular follicles, hypervascular interfollicular regions, or numerous interfollicular plasma cells). Diligent search for atypical or diagnostic Hodgkin’s cells is necessary to rule out co-existent Hodgkin’s disease in the presence of these lesions.

 

H.  Stage                      back     Top     Main Page

In general, TNM classification has not been used for staging the malignant lymphomas because the site of origin of the tumor is often uncertain 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 non-Hodgkin’s lymphoma.  The Ann Arbor classification for lymphomas has been applied to Hodgkin’s lymphoma by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) (see below).  Staging is based on the well established knowledge that Hodgkin’s disease tends to spread in a contiguous fashion from one nodal chain to the next.  The prognosis worsens with progressive spread of disease.(1)

 

Pathologic staging depends on biopsy or resection of one or more regional lymph nodes, splenectomy, wedge and needle liver biopsies, bone marrow biopsy (optional in stages I and II), and biopsy of multiple lymph nodes on both sides of the diaphragm to assess the 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. urinalysis, complete blood examination, and blood chemistry studies), imaging studies (e.g. CAT scans, MRI studies, and nuclear medicine studies) and biopsy to determine diagnosis and histologic type of tumor (initial diagnosis is almost always made on biopsy).

 

There is general agreement that staging of Hodgkin’s disease is prognostically significant.(1,20)

 

AJCC/UICC Stage Definitions for
Hodgkin’s Disease(21)

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.

 

** The number of lymph node regions involved may be indicated by a subscript: e.g. II3. For stage I-IIIA disease, involvement of four or more nodal regions has been shown to adversely affect rates of disease-free survival and overall survival.(1)

 

***For stage IV disease, involvement of more than two extranodal sites has been shown to adversely affect rates of complete response to therapy, disease-free survival, and overall survival.(1)

 

I.  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.

 

J.  Staging Laparotomy             back     Top     Main Page

Staging laparotomy is the gold standard for defining the extent of subclinical disease in the abdomen.  It includes detailed exploration of the abdomen with sampling of the upper abdominal nodes (celiac, splenic hilar, and porta hepatic), the midabdominal nodes (para-aortic and porta caval), and the pelvic nodes (common, external and internal iliac).  In addition, it includes splenectomy and wedge plus needle biopsies of the liver as well as biopsies of any suspicious lesions in the abdomen.(22)

 

In the past decade, the use of staging laparotomy for Hodgkin’s disease has decreased for several reasons: 1) the inherent morbidity of the procedure; 2) the increased accuracy of imaging techniques for predicting positive laparotomy findings; and 3) the use of treatment approaches that do not require knowledge of the extent of subclinical disease.  Nevertheless, a role for staging laparotomy still exists, primarily in patients with favorable disease who may be candidates for management with supradiaphragmatic irradiation alone if the laparotomy reveals no subclinical tumor.(22)

 

In staging laparotomy, thorough examination of spleen is essential since splenic involvement is common but is often inapparent on macroscopic examination. The outer surface is inspected for nodules, and the parenchyma sliced thinly in transverse fashion to be examined for nodular or suspicious lesions. The pathology report should state the number of macroscopically identifiable nodules as well as the microscopic correlation as to the extent of disease.(22)  In stage III Hodgkin’s disease, the amount of tumor in the spleen, specifically four or more tumor nodules, has been shown to adversely affect disease-free survival in patient’s treated with radiation therapy alone.(23) Careful examination of each of the organs and tissues submitted at staging laparotomy and detailed reporting of the extent of involvement by tumor is important to establish the total tumor burden. Measures of tumor burden that combine total extent and volume of tumor in the body have been shown to be highly significant independent prognostic indicators in Hodgkin’s disease.(1,4-5,11-13,23-25)

 

The histologic criteria for involvement by tumor at staging laparotomy are as follows:

 

Lymph nodes and spleen: Same criteria as primary diagnosis

Bone marrow and liver: Mononuclear Reed-Sternberg variants in appropriate cellular background

 

In patients with an established diagnosis of Hodgkin’s disease, granulomas may be found on staging laparotomy in the absence of diagnostic Hodgkin’s cells or variants in lymph nodes, spleen, or bone marrow. Liver may also show nonspecific triaditis. Tissues with these findings are considered free of involvement by Hodgkin’s disease.

 

 

REFERENCES                        back     Top     Main Page

1.     Gospodarowicz MK, Specht L, Sutcliffe SB. Hodgkin’s Disease. In: Hermanek P, Gospodarowicz MK, Henson DE, Hutter RVP, Sobin LH, eds. Prognostic Factors in Cancer. Berlin-New York, Springer-Verlag, 1995.

2.     Haybittle JL, Haygoe FGJ, Easterling MJ, et al. Review of British National Lymphoma Investigation studies of Hodgkin’s disease and development of prognostic index. Lancet. 1985;1:967-972.

3.     Specht L, Nissen NI. Hodgkin’s disease and age. Eur J Hematol. 1989;43:127-135.

4.     Strauss DJ, Gaynor JJ, Myers J, et al. Prognostic factors among 135 adults with newly diagnosed advanced Hodgkin’s disease treated with alternating potentially noncross-resistant chemotherapy and intermediate-dose radiation therapy. J Clin Oncol. 1990;8:1173-1186.

5.     Sutcliffe SB, Gospodarowicz MK, Bergsagel DE, et al. Prognostic groups for management for localized Hodgkin’s disease. J Clin Oncol. 1985;3:393-401.

6.     Mauch P, Goffman T, Rosenthal DS, et al. Stage III Hodgkin’s disease. Improved survival with combined modality therapy as compared with radiation therapy alone. J Clin Oncol. 1985;3:1166-1173.

7.     Anderson H, Jenkins JPR, Brigg DJ, et al. The prognostic significance of mediastinal bulk in patients with stage IA-IVB Hodgkin’s disease: A report from the Manchester Lymphoma Group. Clin Radiol. 1985;36:449-454.

8.     Bonadonna G, Valagussa P, Santoro A. Prognosis of bulky Hodgkin’s disease treated with chemotherapy alone or combined with radiotherapy. Cancer Res. 1985;31:1860-1861.

9.     Pavlovsky S, Maschio M, Santarelli MT, et al. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin’s disease. J Natl Cancer Inst. 1988;80:1466-1473.

10.   Liew KH, Easton D, Horwich A, et al. Bulky mediastinal Hodgkin’s disease management and prognosis. Hematol Oncol. 1984;2:45-59.

11.   Verger E, Easton D, Brada M, et al. Radiotherapy results in laparotomy stage Hodgkin’s disease. Clin Oncol. 1988;39:428-431.

12.   Specht L, Nissen NI. Prognostic factors in Hodgkin’s disease with special reference to tumour burden. Eur J Hematol. 1988:41:80-87.

13.   Specht L, Nordentoft AM, Soren S, et al. Tumor burden as the most important prognostic factor in early stage Hodgkin’s disease. Cancer. 1988:61:1719-1727.

14.   Crnkovich MJ, Leopold K, Hoppe RT, Mauch PM. Stage I to IIB Hodgkin’s disease: The combined experience at Stanford University and the Joint Center for Radiation Therapy. J Clin Oncol. 1987:5:1041-1049.

15.   Hermanak P, Henson DE, Hutter RVP, Sobin LH. TNM Supplement. Berlin-New York, NY: Springer-Verlag NY Inc., 1993.

16.   Specht L. Prognostic factors in Hodgkin’s disease. Cancer Treat Rev. 1991:18;21-53.

17.   Ferry JA, Harris NL. The pathology of Hodgkin’s disease: What’s new? Sem Rad Oncol. 1996;6:121-130.

18.   Chan JKC, Banks PM, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms proposed by the International Lymphoma Study Group. A summary version. Am J Clin Pathol. 1995;103:543-560.

19.   MacLennan KA, Bennett MH, Tu A, et al. Relationship of histopathologic features to survival in nodular sclerosing Hodgkin’s disease. Cancer. 1989;64:1686-1693.

20.   Specht L. Prognostic factors in Hodgkin’s disease. Sem Rad Oncol. 1996;6:146-161.

21.   Fleming ID, Cooper JS, Henson DE, et al., eds. AJCC Manual for Staging of Cancer, 5th ed. Lippincott Raven, Philadelphia, 1997.

22.   Mendenhall NP. Diagnostic procedures and guidelines for the evaluation and follow-up of Hodgkin’s disease. Sem Rad Oncol. 1996;6:131-145.

23.   Hoppe RT, Cox RS, Rosenberg SA, et al. Prognostic factors in pathologic stage III Hodgkin’s disease. Cancer Treat Rep. 1982:66;743-749.

24.   Specht L. Tumour burden as the main indicator of prognosis in Hodgkin’s disease. Eur J Cancer. 1992:28A;1982-1985.

25.   Specht L, Lauritzen AF, Nordentoft AM, et al. Tumour cell concentration and tumour burden in relation to histopathologic subtype and other factors in early stage Hodgkin’s disease. Cancer. 1990:65;2594-2601.

 

 

BIBLIOGRAPHY

•      Collins RD. Lymph node examination: What is an adequate work-up. Arch Pathol Lab Med. 1985;1 09:796-799.

•      Cousar JB. Surgical pathology examination of lymph nodes. Am J Clin Pathol. 1995:104;126-132.

 

 

Authors

Carolyn C. Compton, MD, PhD; Judith A. Ferry, MD; 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; Claire Fung, MD; Nancy L. Harris, MD; Irene Kuter, MD; and Peter Mauch, MD