Procedures
•
Cytology
I.
Cytologic material back Top Main Page
A. Clinical
Information
1. Patient
identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible
physician(s)
3. Date
of procedure
4. Other
clinical information
a. Relevant history
(1) Helicobacter pylori gastritis
(2) gluten enteropathy (celiac disease)
(3) Crohn’s disease
(4) heavy chain disease
(5) AIDS
(6) previous diagnosis and treatment for lymphoma
b. Relevant findings (e.g. endoscopic and/or imaging studies)
c. Clinical diagnosis
d. Procedure (e.g. brushing, washing, other)
e. Operative findings
f. Anatomic site(s) of specimen(s)
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. smear of fluid, cell block)
3. Special
studies (specify) (e.g. flow cytometry for immunophenotyping, cytochemistry,
immunocytochemistry, cytogenetic analysis)
C. Microscopic
Examination
1. Adequacy
of specimen (if unsatisfactory for evaluation, specify reason)
2. Tumor,
if present
a. Histologic type, if possible (Note A)
b. Other characteristics (e.g. nuclear grade, necrosis)
3. Additional
pathologic findings, if present (specify)
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
(endoscopic or other) back Top Main Page
A. Clinical
Information
1. Patient
identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible
physician(s)
3. Date
of procedure
4. Other
clinical information
a. Relevant history
(1) Helicobacter pylori gastritis
(2) gluten enteropathy (celiac disease)
(3) Crohn’s disease
(4) heavy chain disease
(5) AIDS
(6) previous diagnosis and treatment for lymphoma
b. Relevant findings (e.g. endoscopic and/or imaging studies)
c. Clinical diagnosis
d. Procedure (e.g. endoscopic biopsy)
e. Operative findings
f. Anatomic site(s) of specimen(s)
B. Macroscopic
Examination
1. Specimen
a. Fixed/unfixed (specify fixative) [Note: Fresh frozen tissue should
be saved, if possible, for immuno-phenotyping and molecular genetic studies]
b. Orientation
c. Number of pieces
d. Dimensions
e. Obstruction
f. Description of other tissues (as appropriate)
g. Results of intraoperative consultation
2. Submit
all 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 A)
b. Histologic grade
c. Extent of invasion
d. Blood/lymphatic vessel invasion
e. Perineural invasion
2. Additional
pathologic findings, if present
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. Resection of stomach,
small intestine, colon, rectum back
Top
Main
Page
A. Clinical
Information
1. Patient
identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible
physician(s)
3. Date
of procedure
4. Other
clinical information
a. Relevant history
(1) Helicobacter pylori gastritis
(2) gluten enteropathy (celiac disease)
(3) Crohn’s disease
(4) heavy chain disease
(5) AIDS
(6) previous diagnosis and treatment for lymphoma
b. Relevant findings (e.g. endoscopic and/or imaging studies)
c. Clinical diagnosis
d. Procedure (e.g. partial gastrectomy, total gastrectomy, ileal
resection)
e. Operative findings
f. Anatomic site(s) of specimen(s)
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 immuno-phenotyping 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
b. Location
c. Configuration
d. Dimensions (Note B)
e. Descriptive characteristics (e.g. color, consistency)
f. Ulceration/perforation
g. Estimated extent of invasion
h. Penetration of serosa (Note C)
i. Distance from margins (Note D)
(1) proximal
(2) distal
(3) radial (soft tissue or mesenteric margin closest
to deepest tumor penetration)
j. Direct extension to other organ(s) or structure(s) (Note
E)
k. Noncontiguous tumor involvement of other organ(s) or structure(s) (Note E)
3. Additional
pathologic findings, if present
4. Regional
lymph nodes (Note F)
5. Tissues
submitted for microscopic evaluation
a. Lymphoma, representative sections, including:
(1) point of deepest penetration
(2) interface with adjacent mucosa
(3) visceral serosa overlying tumor
(4) soft tissue or mesenteric margin closest to
deepest tumor penetration (radial margin) (Note D)
b. Proximal and distal resection margins
c. Regional lymph nodes
d. Other specific nodes when marked by surgeon
e. Other lesions (e.g. polyps, ulcers)
f. Section(s) of viscus uninvolved by tumor
g. Other tissue(s)/organ(s)
6. Special
studies (specify) (e.g. flow cytometry for immunophenotyping, histochemistry,
immunohistochemistry, cytogenetic analysis)
C. Microscopic
Evaluation
1. Tumor
a. Histologic type (Note A)
b. Histologic grade
c. Extent of invasion
d. Penetration of serosa (Note C)
e. Margins (Note D)
f. Direct extension to other organ(s) or structure(s) (Note
E)
2. Regional
lymph nodes (Note F)
a. Number
b. Number involved by tumor (Note G)
3. Extraregional
lymph nodes
a. Number
b. Number involved by tumor (Note G)
4.
Other tissues submitted (if distant involvement
by lymphoma, specify site) (Note G)
5. Additional
pathologic findings, if present
a. Chronic gastritis with or without Helicobacter pylori infection
b. Celiac disease
c. Inflammatory bowel disease
d. Lymphoid hyperplasia
6. Results/status
of special studies
7. 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. Histologic Type back
Top Main
Page
Hodgkin’s Disease
Hodgkin’s disease is
divided into four major histologic types. Histologic classification is based on
paraffin-embedded, hematoxylin and eosin-stained sections. The histologic types
should be recorded because they may have prognostic significance. Primary
Hodgkin’s disease of the gastrointestinal tract is exceptionally rare.
Immunopheno-typing and, if necessary, genetic studies (i.e. gene rearrangement)
should be performed to confirm the diagnosis and to exclude non-Hodgkin’s
lymphoma.
Histologic
Classification of Hodgkin’s Disease
• Lymphocyte predominance, nodular
• Nodular sclerosis
• Mixed cellularity
• Lymphocyte depletion
• Unclassified
Non-Hodgkin’s Lymphoma
Controversy currently
exists as to whether the spectrum of lymphomas found in the gut can be
adequately accommodated within the conventional classifications (see below) or
whether a site-specific classification of gastrointestinal lymphomas is needed.
In contrast to nodal lymphomas, many lymphomas of the gastrointestinal tract
are derived from mucosa-associated lymphoid tissue (MALT) which they resemble
histologically. In further contrast to nodal lymphomas, they tend to be
localized at the time of diagnosis and may be effectively treated with local
therapy. MALT-derived lymphomas are sometimes referred to by the unscientific and
imprecise term of “MALToma.” Some of these tumors have unique etiologic
associations (e.g. gastric B cell lymphoma of MALT type and infection by
Helicobacter pylori). Unique etiologic associations also exist between gluten
enteropathy and primary T cell lymphomas of the gastrointestinal tract. In
addition, nodal-type lymphomas (e.g. Burkitt’s, mantle cell, follicle center
lymphomas) may also present in gastrointestinal tract.
Because neither the
B-cell lymphomas of the MALT type nor the enteropathy-associated T-cell
lymphomas are features of current standard classifications of non-Hodgkin’s
lymphoma, the protocol recommends the most recently proposed classification of
the International Lymphoma Study Group (i.e. the Revised European-American
Lymphoma Classification) [REAL], which incorporates these entities as well as
other types of gastrointestinal lymphomas with unique clinical associations.
The REAL classification encompasses both nodal and extranodal lymphomas and
outlines the immunobiologic features of the defined entities that aid in the
diagnosis.(1,2) These concepts have also been incorporated into the
classification of primary gastrointestinal lymphoma proposed by Isaacson.(3)
Both of these classifications are shown below.
Prognostic information
necessary to determine treatment of gastrointestinal lymphomas is provided by
the histologic type. Further sorting of these diseases into broad histologic
grades or clinical prognostic groups provides little additional useful information.
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 (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 gd 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
* Primary
gastrointestinal mantle cell lymphoma is associated with a growth pattern of
lymphomatous polyposis. Immunophenotype: sIgM+, sIgD+, lambda>kappa, Pan B+,
CD5+, CD10-/+, CD23-, CD43+, CD11c-, CD25-, ill-defined loose or expanded
follicular dendritic cell meshworks in 80%. Genetics: IgH and IgL genes
rearranged: t(11;14); rearranged bcl-1 gene (CCND1/cyclin D1/PRAD1) common.
** Immunophenotype:
sIg+ (IgM or IgA or IgG), sIgD-, clg-/+, Pan B+, CD5-, CD10-, CD23-, CD43-/+.
Genetics: IgH and IgL genes rearranged; bcl-1 and bcl-2 germline; Trisomy 3 or
t(11;18)(q21;q21) may be seen.
*** Extranodal
occurrence (e.g. gastrointestinal tract) in 40% of cases overall.
Immunophenotype: sIg+/-, clg+, Pan B+, CD45+/-, CD5-/+, CD10-/+(weak).
Genetics: IgH and IgL genes rearranged: bcl-2 gene rearranged in 30%;
bcl-6/LAZ3 gene (chromosome 3q27) rearranged in 30%, rearranged c-myc gene
uncommon. About 25% of gastric large B cell lymphomas have associated low grade
MALToma.
**** Immunophenotype:
sIgM+, Pan B+, CD5-, CD10+(strong). Genetics: IgH and IgL genes rearranged;
t(8;14) and variations including t(2;8) and t(8;22); rearranged c-myc gene. EBV
common (95%) in endemic cases, infrequent (15% to 20%) in sporadic cases,
intermediate occurrence (30% to 40%) in HIV-positive cases.
***** Immunophenotype:
TdT-, CD3+, CD7+, CD4-, CD8+/-, CD103+ (mucosal lymphocyte antigen as detected
by HML-1). Genetics: TCR genes rearranged.
Histological
Classification of Primary
Gastrointestinal Lymphoma
B Cell
• MALT type
- Low
grade†
- High
grade with or without a low-grade
component†
• Immunoproliferative small intestinal
disease
(IPSID)
- Low
grade
- High
grade with or without a low-grade
component
• Mantle cell (lymphomatous polyposis)
• Burkitt’s and Burkitt-like
• Other types of low- or high-grade lymphoma
corresponding to lymph node
equivalents
T Cell
• Enteropathy-associated T-cell lymphoma
(EATL)
• Other types unassociated with enteropathy
Rare types (including
conditions that may simulate lymphoma such as histiocytic neoplasms and
granulocytic sarcoma)
† Equivalent entity
within the REAL classification (see above): extranodal marginal zone B-cell
lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type).
The term MALT lymphoma (“MALToma”) should be restricted to histologically
low-grade B-cell lymphoma of MALT type. High-grade B-cell lymphoma of the
gastrointestinal tract should be referred to as diffuse-B large- cell lymphoma
(with or without a residual low-grade component).
Other
Classifications
For other current
histologic classifications of non-Hodgkin’s lymphoma (Working Formulation,
Kiel) used in the literature on gastrointestinal lymphoma.
B. Tumor Dimensions back
Top Main
Page
The largest tumor
dimension has been shown to have independent prognostic significance, with size
<5 cm constituting a favorable prognostic factor.(4-6)
C. Serosal Penetration by Tumor back Top Main Page
The serosal
penetration by tumor has been shown to be an adverse prognostic factor.(7-10)
D.
Resection Margins back
Top Main
Page
Includes the proximal,
distal, and radial margins. The radial margin represents the nonperitoneal soft
tissue or mesenteric margin closest to the deepest penetration of tumor.Although
controversial, involvement of surgical margins by tumor may correlate with
decreased survival.(5,11) In some institutions,
adjuvant radiation and/or chemotherapy may be used in those cases in which
tumor is found to be present at the surgical resection margins.(5,12)
In low-grade gastric
B-cell lymphomas of MALT, small foci of lymphoma consisting of 1-4 lymphoid
follicles surrounded by neoplastic marginal zone B cells may be found
throughout the gastric mucosa at various distances from the main confluent
tumor mass and from each other.(13) This phenomenon may contribute
to local relapse within the gastric stump in cases in which the resection
margins are negative by microscopic examination.
E. Involvement of Adjacent Structures by Tumor back Top Main Page
Direct penetration of
adjacent structures by tumor has been shown to have independent adverse
prognostic significance.(5)
F.
Regional Lymph Node by Site back Top Main Page
STOMACH: perigastric
nodes along the lesser and greater curvature, nodes located along the left
gastric, common hepatic, splenic, and celiac arteries.
DUODENUM: duodenal,
hepatic, pancreaticoduodenal, infrapyloric, gastroduodenal, ampulla of Vater,
pyloric, cystic, superior mesenteric, hilar, pericoledochal.
JEJUNUM / ILEUM:
superior mesenteric, mesenteric, posterior cecal (terminal ileum only),
ileocolic (terminal ileum only).
LARGE INTESTINE:
• Cecum and appendix — anterior cecal,
posterior cecal, ileocolic, right colic
• Ascending colon — ileocolic, right colic,
middle colic
• Hepatic flexure — middle colic, right
colic
• Transverse colon — middle colic
• Splenic flexure — middle colic, left
colic, inferior mesenteric
• Descending colon — left colic, inferior
mesenteric, sigmoid
• Sigmoid colon — inferior mesenteric,
superior rectal sigmoidal, sigmoid mesenteric
• Rectosigmoid — perirectal, left colic,
sigmoid mesenteric, sigmoidal, inferior mesenteric, superior rectal, middle
rectal
• Rectum — perirectal, sigmoid mesenteric,
inferior mesenteric, lateral sacral, presacral, internal iliac, sacral
promontory, superior rectal, middle rectal, inferior rectal
In general, the TNM
classification has not been used for staging the malignant lymphomas because
the site of origin of the tumor is often unclear and there is no way to
differentiate among T, N, and M category. 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 extranodal
lymphomas by the American Joint Committee on Cancer (AJCC) and the International
Union Against Cancer (UICC) (see below).(14-16) The Ann Arbor System
has also been modified specifically for primary gastrointestinal lymphomas by
Musshoff.(17) Both systems are shown below.
Pathologic staging
depends on biopsy or resection of the primary mucosal site, biopsy or resection
of one or more regional lymph nodes, splenectomy, wedge liver biopsy, bone
marrow biopsy, and 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, progressing
sequentially from less invasive to more invasive, and includes medical history,
physical examination, laboratory tests (e.g. urinalysis, complete blood
examination, and blood chemistry studies), imaging studies (e.g. CAT scans, GI
series) and biopsy to determine diagnosis and histologic type of tumor (initial
diagnosis is almost always made on biopsy).
There is almost
universal agreement that staging of gastrointestinal lymphoma is prognostically
significant.(4,5,7-11,19,20)
Staging
for Primary Extralymphatic Lymphomas
Stage I Localized involvement of a single extralymphatic
organ or site (IE)*
Stage II Localized involvement of a single 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 Localized involvement of a single extralymphatic
organ or site with involvement of lymph node regions on both sides of the
diaphragm (IIIE) or
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*,**
* Direct spread of a
lymphoma into adjacent tissues or organs does not influence stage. Multifocal
involvement of a single extralymphatic organ is classified as stage IE and not
stage IV. Involvement of two or more segments of the gastrointestinal tract,
isolated and not in continuity, is classified as stage IV (disseminated
involvement of one or more extralymphatic organs).
** The definitions of
regional lymph nodes for individual sites of extranodal lymphomas are identical
to the definitions of regional lymph nodes for individual sites of
gastrointestinal carcinomas. For example, the regional lymph nodes for a
primary gastric lymphoma are the perigastric nodes along the lesser and greater
curvatures and the nodes located along the left gastric, common hepatic,
splenic, and celiac arteries.
Modified
Ann Arbor Staging System for
Gastrointestinal Lymphoma(17)
Stage I Tumor confined to the gastrointestinal tract
(IE)*
Stage II Tumor with spread to regional lymph nodes
(IIE1) or tumor with nodal involvement beyond regional lymph nodes (IIE2)*,**
Stage III- Tumor with spread to other organs
IV within the abdomen (liver,
spleen) or beyond the abdomen (chest, bone marrow)*,**
* Direct spread of a
lymphoma into adjacent tissues or organs does not influence stage. Multifocal
involvement of a single extralymphatic organ is classified as stage IE and not
stage IV. Involvement of two or more segments of the gastrointestinal tract,
isolated and not in continuity, is classified as stage IV (disseminated
involvement of one or more extralymphatic organs).
** The definitions of
regional lymph nodes for individual sites of extranodal lymphomas are identical
to the definitions of regional lymph nodes for individual sites of
gastrointestinal carcinomas. For example, the regional lymph nodes for a
primary gastric lymphoma are the perigastric nodes along the lesser and greater
curvatures and the nodes located along the left gastric, common hepatic,
splenic, and celiac arteries.
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Harris NL, Jaffe ES, Stein H, et al. A
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6.
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Shiu MH, Nisce LZ, Pinna A, Straus DJ,
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Musshoff K, Schmidt-Vollmer H. Prognosis
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Cogliatti SB, Schmid U, Shumacher U, et
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Authors
Carolyn
Compton, MD, PhD and Leslie H. Sobin, MD
©1998.
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.
2 Originally published in the Archives of
Pathology & Laboratory Medicine, October 1997.
2 Contributors: back
Top Main
Page
CAP Cancer Committee; Donald Antonioli, MD; Harvey Goldman, MD; Rodger C.
Haggitt, MD;
Nancy L. Harris, MD; Robert V. P. Hutter,
MD;
J. Milburn Jessup, MD; Klaus Lewin, MD;
Pablo Ross, MD; Heidrun Rotterdam, MD;
Stuart Spechler, MD; Miriam E. Vincent, MD;
Christopher Willett, MD; Donald E. Henson, MD