Article

Handling and pathology reporting of specimens with carcinoma of the urinary bladder, ureter, and renal pelvis. A joint proposal of the European Society of Uropathology and the Uropathology Working Group

Università degli Studi di Palermo, Palermo, Sicily, Italy
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (Impact Factor: 2.65). 09/2004; 445(2):103-10. DOI: 10.1007/s00428-004-1039-8
Source: PubMed

ABSTRACT

Pathologists play a pivotal role in the diagnosis and in the report of the pathological features related to prognosis. To meet these endpoints, the following issues must be addressed: adequate information about the patient history, proper handling of the specimens, identification of the reliable histopathological techniques necessary to reach the more detailed diagnostic information and evaluation of the prognostic variables, and standardized pathological reporting. In this review we discuss a proposal for standardization of sampling and reporting of the urothelial tissues achieved within uropathology. The urologists have a great role in assisting pathologists in the proper examination by providing them with clinical information.

Virchows Arch (2004) 445:103–110
DOI 10.1007/s00428-004-1039-8
REVIEW ARTICLE
Antonio Lopez-Beltran · Pier Francesco Bassi ·
Michele Pavone-Macaluso · Rodolfo Montironi
Handling and pathology reporting of specimens with carcinoma
of the urinary bladder, ureter, and renal pelvis.
A joint proposal of the European Society of Uropathology
and the Uropathology Working Group
Received: 21 January 2004 / Accepted: 22 April 2004 / Published online: 8 June 2004
Springer-Verlag 2004
Abstract Pathologists play a pivotal role in the diagnosis
and in the report of the pathological features related to
progn osis. To meet these endpoin ts, the following issues
must be addressed: adequate information about the pa-
tient history, p roper handling of the specimens, identifi-
cation of the reliable histopathological techniques nec-
essary to re ach the more de tailed diagnostic informa-
tion and evalua tion of the prognostic variables, and
standardized pathologi cal reporting. In this review we
discuss a proposal for standardization of sampling and
reporting of the ur othelial tissues achieved w ithin uro-
pathology. The urologists have a great role in assisting
pathologists in the proper exami nation by prov iding them
with clinical information.
Keywords Bladder · Ureter · Pelvis · Neoplasms ·
Transitional cell · Squamous carcinoma ·
Adenocarcinoma · Pathology report · Sampling ·
Standardization
Introduction
The urothelium covers the urinary tract from the kidney
calyces, renal pelvis, ureter, urinary bladder, and a vari-
able portion of the urethra. Most carcinomas of these
organs are histologically similar [3]. Surgical procedures
of these organs provide an important number of speci-
mens in clinical practice [20]. An appropriate assessment
of the specimens and reporting of pathological findings
may assist urologists in the appropriate management of
patients [20].
The most common bladder specimens are obtained
from endoscopic biopsies and transurethral resections of
the bladder (TURB), both of which sample subepithelial
tissue of varying depth [12]. Other specimens can be
obtained from a cystectomy (partial/total), cystoprostate-
ctomy, pelvic exanteration (“en block” resection), and
resection of diverticula [12]. Surgical excision of an
urachal carcinoma usually includes the bladder dome,
urachus, and umbilicus [12].
A bladder biopsy provides information to assess risk
factors for recurrence, progression, and response to treat-
ment [2, 16, 17, 18, 23, 28] (Table 1). Small, noninvasive
papillary neoplasms are often excised using biopsy with
cold-cup forceps, diathermy forceps, or a small diathermy
loop. To avoid tissue distortion, these specimens should be
A. Lopez-Beltran (
)
)
Unit of Anatomic Pathology, Faculty of Medicine,
Avda. Menendez-Pidal S/N, 14004 Cordoba, Spain
e-mail: em1lobea@uco.es
Tel.: +34-957-218993
Fax: +34-957-218229
P. F. Bassi
Department of Urology, University of Padova Medical School,
Padova, Italy
M. Pavone-Macaluso
Clinica Urologica, Universit di Palermo,
Palermo, Italy
R. Montironi
Institute of Pathological Anatomy,
Polytechnic University of the Marche Region (Ancona),
Ancona, Italy
Table 1 Current prognostic factors in bladder cancer specimens
Number of tumors
Cancer size >5 cm in diameter
Tumor extent (stage)
Histological grade
Coexistent dysplasia or carcinoma in situ
Tumor growth pattern
Vascular/lymphatic invasion
Lymph-node involvement
Recurrence at 3 month follow-up cystoscopy
Molecular markers (p53, RB, cadherins)
Others: DNA ploidy, Ki67-MIB1
Page 1
transferred to fixative with minimal handling [12, 20].
Larger neoplasms are often sampled using TURB with a
diathermy loop that produces strips of tissue 6 mm in
diameter and of variable length [14]. Additional resection
of the bladder base after a previous TURB provides ad-
ditional information on tumor extension. All hyperemic or
velvety areas of urothelium are sampled to exclude car-
cinoma in situ (CIS); random biopsies are commonly
taken from macroscopically normal urothelium distant
from the tumor site to determine the extent of involvement
[25, 32]. Ideally, random samples should be obtained from
predetermined sites in four vesical quadrants [25]. Some
urologists also submit biopsy specimens of the urethra to
assess other areas of the urothelium, particularly in pa-
tients with high-grade papillary urothelial carcinoma or
CIS [1]. Nephroureterectomy or ureterectomy specimens
are the result of cancer in these organs. This article re-
views the handling and pathology reporting of bladder,
ureter and renal pelvis specimens with tumor.
Role of the urologist
Urologists play a capital role in uropathology practice
[25, 28], since they are responsible for providing the pa-
thologist with adequate tissue samples for pathological
evaluation and handling the biopsies in a way that will
enable the pathologist to give the urologist an overall
assessment of the neoplasia and the resections margins
[30, 31]. Also, it is of great importance to provide the
pathologist with all useful clinical information (Table 2).
Role of the pathologist
Handling of specimens
Routine protocol-based tissue sampling ensures consistent
and thorough examination by trainees and consultants.
The issue has been addressed in the last few years by
different groups and societies, among which are the As-
sociation of Directors of Anatomic Pathology and the
College of American Pathologists [2, 30, 31]. The con-
clusions of each of these contemporary statements have
been incorporated to create a standardized approach to
examination of tumor specimens obtained from the blad-
der, ureter, and renal pelvis [20]. The recommendations
are related to the nature of specimens, that is: bladder
biopsy and TURB [1, 5, 9, 10, 14, 18, 20, 21, 22, 25, 27,
33, 36] (Table 3); total cystectomy, radical cystoprosta-
tectomy, pelvic exanteration, and partial cystectomy [1, 3,
8, 12, 18, 19, 20, 21, 23, 24, 26, 30, 31] (Table 4) (see also
Appendix no. 1, Appendix no. 2, and Appendix no. 3);
and ureterectomy or nephroureterectomy specimens [12]
(Table 5).
Diagnostic reporting of pathological findings
The pathology report should include clinically relevant
information as well as provide clinically useful informa-
tion derived from the macroscopic examination and mi-
croscopic evaluation.
Table 2 Role of the urologist in
handling urological specimens
with tumor
To provide with appropriate clinical information, mainly:
Urological and non-urological disease
Previous treatments
To handle the biopsies/surgical specimens in a way to allow an overall assessment of the neoplasia and
resection margins
To provide adequate tissue samples for pathological evaluation:
To resect a tumor superficially
To resect more deeply (including suburothelial connective tissues and superficial detrusor muscle)
Random biopsies of endoscopically normal urothelium and the prostatic urethra in case of a multi-
focal tumor
For small and single primary tumor, the random biopsies are not routinely recommended if urine
cytology is negative
To submit all of the pieces of tissue for processing and multiple sectioning
To avoid unnecessary delay in bladder fixation in specific situations, the urologist himself can
open the bladder from the urethra to the bladder dome using scissors and then fix it in formalin
Table 3 Handling and reporting of bladder biopsy and transurethral resections of the bladder (TURB) specimens
Specimens vary from single and minute to numerous and large, and orientation is generally difficult. Record the number, size, and
epithelial proliferations when present. Report intraepithelial lesions, and, if present, report “denuded biopsy” (most probably related to
carcinoma in situ)
Avoid the “common mistake” of overfilling specimen cassettes
Transurethral resections should be weighted in aggregate, and each submitted specimen should receive separate diagnosis
The presence or absence of detrusor muscle in the sample should be stated in the final report. Care must be taken to distinguish the
muscularis mucosae bundles within the subepithelial connective tissue from the detrusor muscle. Immunohistochemical staining can
help in selected cases
Provide the tumor node metastasis staging system. In TURB specimens showing muscularis propria invasion, the only reasonable
statement is “stage T2 at least”. Fat tissue in biopsy specimens is not an indication of extravesical extension, since fat may be present
within the bladder wall
In TURB specimens, embedding all the resected tissue chips may be necessary in selected cases
104
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Histological tumor type
More than 95% of carcinomas of the urinary bladder,
ureter, and renal pelvis are urothelial. Focal squamous
and/or glandular differentiation may be present in the tu-
mor (mixed differentiation), an aspect that must be clearly
reported. Pure squamous or adenocarcinomas may also
arise in these organs, as well as other unusual histological
variants of urothelial carcinoma [7, 22] (Table 6).
Histological grade
There is significant controversy over the classification
and grading of these tumors [4, 6, 28]. Papillary and in-
vasive lesions are graded separately. Due to the different
classification systems available and the need for a uni-
versally acceptable system, in 1998, the World Health
Organization (WHO) and the International Society of
Urological Pathology (ISUP) proposed a consensus clas-
Table 4 Handling and reporting of total cystectomy, radical cystoprostatectomy, pelvic exanteration and partial cystectomy specimens
Orientation of the specimen
The peritoneum can be used as reliable anatomic landmark. It descends further along the posterior wall of the bladder than it does
along the anterior wall. Other pelvic organs can also be used if present. Locate both ureters (lateral perivesical fatty connective tissues)
and, when present, the vasa deferentia
Fixation of the specimen
Fixation of the bladder must be performed as soon as possible; formalin is widely used but other fixatives should be considered in specific
situations (i.e., molecular studies)
Dissection of the specimen (see also Appendix no. 1)
Once the specimen is open, the bladder mucosal surface is examined for ulcerations or tumors. Size, gross morphology (flat, papil-
lary, nodular, or ulcerated), and location (e.g., dome, trigone, free walls, and so on) of any lesion in the bladder are noted
Photograph(s) of the opened specimen are taken, if necessary. Fresh tissue may be collected for special studies by the urologist or,
preferably by the pathologist, but this must be stated in the pathological report
Then shave the margins from each of the ureters and the urethra. When the specimen includes the prostate, this distal urethral margin
should be taken from the distal end of the prostate
Next, beginning at their trigone orifices open the ureters on both sides using a small pair of scissors. Look for ureteral strictures and
dilatations. Examine the mucosa for ulcerations, diverticula or exophytic lesions and document these findings. Submit transverse sections
of the ureters
If a tumor is identified in the bladder, make a full-thickness cut through the tumor and bladder wall. See whether or not the tumor
appears to infiltrate the muscularis propria and, if so, whether it extends into the perivesical fat or other anatomic structures. Take sections
of the tumor to demonstrate its relationship to the adjacent urothelium and its maximal depth of invasion. In large exophytic tumors,
sections will be more informative when they are taken from the base of the tumor
Carefully inspect and sample the normal appearing bladder mucosa. Be sure to search for lymph nodes, which are sometimes present
in the perivesical fat (see Appendix no. 2)
Prostate examination will be performed according to the standard rules for pathological evaluation and reporting for radical prosta-
tectomy. Similarly, uterus, rectum, and vagina will be evaluated according to standardized criteria. Section these structures to document
their presence and demonstrate the relationship between the tumor and each of these structures. Evaluate the resection margins for each
organ and record other primary diseases (see Appendix no. 3)
Partial cystectomy specimen
Partial cystectomy specimens (including resections of diverticula) should be fixed and dissected according to the guidelines given
for complete bladder specimens. The edges of the specimen represent the surgical margins of the bladder wall
Ink the edges and assess these margins for tumor involvement by taking perpendicular sections from all edges of the specimen at
regular intervals. Remember to include mucosa as well as the bladder wall
A variation of the partial cystectomy is seen in resections of neoplasms arising from the urachal tract. These specimens consist of
the dome of the bladder in continuity with the urachal tract up to and including the umbilicus. In particular:
Sections should be taken at right angles to the long axis of the urachal tract. Submit a number of these cross sections from the ura-
chal tract for histology as well as the standard sections for the bladder portion
Remember to sample the two additional margins introduced by this resection: the soft tissue margin surrounding the urachus and the
skin margin around the umbilicus
Table 5 Handling and reporting of nephro-ureterectomy or ureterectomy specimens with tumor
Nephro-ureterectomy
Begin the dissection at the kidney hilum and identify the ureter, renal artery, and renal vein
Bivalve the kidney so that the relationship of the tumor of the renal pelvis or the calyces of the upper and lower poles can be easily
visualized. In general, it will be a sagittal cut that begins at the hilum and exits laterally trough the perinephric fat
Obtain enough tissue sections to show the tumor and its relationship with renal parenchyma and peri-pelvic soft tissues
Record size of the tumor and if papillary or solid. At histology, describe type, grade, and stage. Submit sections that include the tumor,
the adjacent non-neoplastic kidney and distal ureter
Ureterectomy specimen
Submit both margins for separate evaluation and then open the entire ureter with a pair of scissors. Carefully inspect the mucosa and
wall
Report the gross characteristics of the ureter and of the tumor
Record the size of the tumor and if it is papillary or solid, invasive or non-invasive, and if the surgical margin or peri-ureteric soft tissues
are affected
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sification known as the WHO/ISUP classification [9].
This has recently been recognized as the WHO 2004
histological classification of non-invasive papillary uro-
thelial tumors [37] (Table 6). Until the WHO 2004
system is clinically and prognostically validated, tumor
grade according to both the WHO 2004 system and the
previous WHO (1973) [29] system should be used, for
instance, papillary urothelial neoplasm of low malignant
potential (WHO 2004)/transitional-cell (urothelial) carci-
noma, grade I (WHO, 1973).
Tumor-growth pattern
The most important morphology-based prognostic factors
in patients with advanced bladder cancer are tumor stage
and lymph-node status. With regard to tumor grade, re-
cent studies have failed to demonstrate a significant prog-
nostic impact in muscle-invasive bladder cancer. In an
attempt to identify new parameters allowing one to assess
prognosis in bladder cancer patients more accurately,
Jimenez et al. have recently introduced a new morpho-
logical classification, distinguishing three patterns of
growth (nodular, trabecular, and infiltrative type) [13].
Tumors with an infiltrative growth pattern are associated
with worse prognosis in comparison with a tumor dis-
playing a non-infiltrative growth pattern. Morphologi-
cally, the three patterns are as follows.
Nodular pattern. Tumor is growing as well-demarcat-
ed, round nests of cells. The nests vary in diameter, but
display a tendency toward roundness. Desmoplasia is
usually inconspicuous. Necrosis is uncommon.
Trabecular pattern. Tumor is composed of infiltrating
broad trabeculae usually anastomosing with each oth-
er. The trabeculae are at least three cell layers thick
and are sometimes associated with extensive necrosis
and desmoplastic stroma.
Infiltrative pattern. Tumor composed of infiltrating
narrow cords or single cells. Desmoplasia and necro-
sis are common. The cells are highly pleomorphic or
small and morphologically undifferentiated.
Tumor extent
The definition of the tumor extent requires knowledge of
the components of the organ and its relationship with
the adjacent structures. For instance, the urinary bladder
consists of three layers.
Epithelium and sub-epithelial connective tissue that is
the lamina propria or submucosa when muscularis
mucosae is present (up to 94% of bladders).
Muscularis propria (or detrusor muscle).
The peri-vesical fat (peritoneum covering the superior
surface and upper part). The bladder is located ex-
traperitoneally.
A critical role of the pathologist is to diagnose the
depth and extent of invasion breaking down a distinction
between bladder mucosa (Ta), suburothelial connective
tissue (T1), detrusor muscle (T2), or beyond (T3 or T4).
The TNM (tumor node metastasis) Staging System, 2002
revision, for carcinomas of the urinary bladder, ureter,
and renal pelvis of the American Joint Committee on Can-
cer (AJCC)/International Union Against Cancer (UICC)
is recommended [10] (Table 7). The corresponding pT
(pathological tumor stage) category must be applied only
to the surgical (cystectomy) specimens.
Table 6 Histological type of tumors of the urinary bladder, ureter,
and renal pelvis (World Health Organization, 2004) [22, 37]
Urothelial neoplasia
Benign
Urothelial papilloma
Inverted papilloma
Papillary urothelial neoplasia of low malignant potential
Malignant papillary
Papillary carcinoma, low grade
Papillary carcinoma, high grade
Papillary carcinoma with squamous or glandular differentiation
Malignant non-papillary
Flat carcinoma in situ
Invasive carcinoma
Variants of invasive carcinoma
Nested pattern
Small tubular patter
Microcystic pattern
Inverted pattern
With squamous differentiation
With glandular differentiation
Micropapillary
Sarcomatoid carcinoma
Clear-cell urothelial carcinoma
Plasmocytoid
With syncitiotrophoblasts
With unusual stromal reactions
Pseudosarcomatous stroma
Stromal osseous or cartilaginous metaplasia
Osteoclast-type giant cells
With prominent lymphoid infiltrate
Squamous-cell carcinoma
Usual type
Variant
Verrucous
Basaloid
With sarcomatoid features
Adenocarcinoma (from bladder mucosa, urachal, with extrophy)
Usual intestinal type
Mucinous (including colloid)
Signet-ring cell
Clear cell
Hepatoid
Mixture of above patterns
Adenocarcinoma not otherwise specified
Tumors of mixed cell types
*Undifferentiated carcinomas
Small-cell carcinoma
Large-cell neuroendocrine carcinoma
Lymphoepithelioma-like carcinoma
Giant-cell carcinoma
Undifferentiated carcinoma not otherwise specified
Metastatic carcinoma
* Refers to tumors that are undifferentiated by light microscopy
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The pathologist must pay attention to diagnose tumor
infiltrating the sub-epithelial connective tissue (T1); this
diagnosis should be supported in uncertain cases using
immunohistochemical studies [14, 15, 27]. T1 substaging
based on the relationship of the tumor with the muscularis
mucosae is not universally accepted, even though evi-
dence seems to support its clinical value.
Designation of a tumor as merely muscle invasive is
inappropriate: the type of muscle invasion, i.e., muscu-
laris mucosae (T1 tumors) versus detrusor muscle (T2
tumors) invasion, needs to be clearly stated [14]. De-
scriptive terminology, such as “urothelial carcinoma with
muscle invasion, indeterminate for type of muscle inva-
sion,” may be used when it is not possible to assess the
type of muscle invaded by the tumor (muscularis mucosae
or detrusor muscle). A comment on thermocoagulation
effect may be reported if it makes diagnostic evaluation
difficult.
Tumor size and multicentricity
In surgical specimens, the pathology report has to include
the size of the tumor and information on its multicen-
tricity, especially when dealing with bladder specimens.
Tumor size affects tumor invasiveness. Of lesions that are
larger than 5 cm, 35% will progress to muscularis propria
invasion, whereas only 9% of tumors smaller than 5 cm
progress similarly. In some studies, the presence of mul-
tiple tumors affects recurrence rates but does not affect
the likelihood for invasion, whereas other studies have
shown an association with progression of disease [18].
Margins
Tumors involving the resection margin on pathological
examination may be assumed to correspond to residual
tumor in the patient and may be classified as macroscopic
or microscopic according to the findings at the specimen
margin(s). The resection margin status should be carefully
specified. In particular:
Table 7 TNM (tumor node
metastasis) staging system
(AJCC/UICC, 2002) of the uri-
nary bladder, renal pelvis, and
ureter [10]
Primary tumor (T): urinary bladder
TX Primary tumor can not be assessed
T0 No evidence of primary tumor
Ta Papillary non-invasive carcinoma
Tis Carcinoma in situ: “flat tumor”
T1 Tumor invades sub-epithelial connective tissue
T2 Tumor invades muscle
T2a Tumor invades superficial muscle (inner half)
T2b Tumor invades deep muscle (outer half)
T3 Tumor invades perivesical tissue
T3a Microscopically
T3b Macroscopically (extra-vesical mass)
T4 Tumor invades any of the following: prostate, uterus, vagina, pelvic wall,
and abdominal wall
T4a Tumor invades prostate or uterus or vagina
T4b Tumor invades pelvic wall or abdominal wall
Primary tumor (T): renal pelvis and ureter
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Ta Papillary noninvasive carcinoma
Tis Carcinoma in situ
T1 Tumor invades subepithelial connective tissue
T2 Tumor invades the muscularis
T3 For renal pelvis only: tumor invades beyond muscularis into peripelvic fat or
the renal parenchyma
T3 For ureter only: tumor invades beyond muscularis into periureteric fat
T4 Tumor invades adjacent organs, or through the kidney into the perinephric fat
The suffix “m” should be added to the appropriate T category to indicate multiple tumors.
The suffix “is” may be added to any T to indicate the presence of associated carcinoma
in situ
Regional lymph nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastases in a single lymph node, 2 cm or less in greatest dimension
N2 Metastases in a single lymph node, more than 2 cm but not more than 5 cm in
greatest dimension, or multiple lymph nodes, none more than 5 cm in greatest
dimension
N3 Metastasis in a lymph node more than 5 cm in greatest dimension
Distant metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
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Statements about deep soft tissue margins should
specify whether peritoneal surfaces are involved with
the tumor
In cases of urachal adenocarcinoma in which partial
cystectomy with excision of the urachal tract and
umbilicus is performed, the margins of the urachal
tract, i.e., the soft tissue surrounding the urachus and
the skin around the umbilical margin, should be spec-
ified
In renal pelvis, ureter, and nephroureterectomy speci-
mens, the margins may include radial hilar soft tissue
margin, bladder cuff, ureteral, renal parenchyma, and
Gerota’s fascia margins, depending on the type of
surgical specimen
Venous/lym phatic vascular invasion
Urothelial carcinoma may invade blood vessels or lym-
phatic channels. In suspicious cases, blood vessels can be
highlighted using immunohistochemical staining for fac-
tor-VIII-related antigen, CD31, or CD34 [35]. Staining
will not resolve the problem of differentiating lymphatic
versus artifactual space entrapment by tumor cells in
some cases. Retraction artifact is also prominent in the
“micropapillary variant” of urothelial carcinoma.
Urothelial carcinoma in situ
The evaluation of urothelium in patients who have su-
perficial (stage Ta or T1) tumors is important because
those patients who have associated CIS are at higher risk
of tumor recurrence and disease progression [14].
Additional information
Additional information (epidemiological, morphological,
and molecular or genetic abnormalities) can be reported
by the pathologist (Table 8). For instance, urothelial
carcinoma has been studied extensively on a biological
(molecular or genetic) basis. Prognostic factors identified
from such studies have been proposed and include blood-
group antigen expression in tumor cells, measurement of
proliferative activity by DNA content analysis and S-
phase fraction, and proliferation markers. Immunohisto-
chemical analysis has been used to detect abnormal gene
products. Multiple genetic changes are associated with
bladder carcinoma and are detected by karyotyping, flu-
orescent in situ hybridization, restriction-fragment-length
polymorphisms, and microsatellite analysis. There is no
consensus in the current literature about the definitive role
and value of such prognostic factors [11, 15, 34].
Acknowledgements This publication is made under the auspices of
the European Society of Uropathology (a full section office mem-
ber of the European Association of Urology, EAU) and the
Uropathology Working Group (European Society of Pathology,
ESP). It is based on the Uropathology Workshop held in Sesto
Fiorentino (Ely Lilly Italia Headquarter), Florence, Italy, 15 June
2003.
Appendix no. 1
Sections for microscopic evaluation
(with special reference to bladder)
In transurethral resections of the bladder specimens,
submit one section per centimeter of tumor diameter (up
to ten cassettes). If the tumor is noninvasive by the initial
sampling, additional submission of tissue (including pos-
sibly submitting all tissue) is necessary to diagnose or rule
out the presence of invasion. If tumor is invasive into the
lamina propria in the initial sampling, additional sections
(including possibly submitting the entire specimen) may
be necessary to diagnose or rule out the possibility of
muscularis propria invasion.
In cystectomy specimens, several representative sec-
tions of the tumor, including the macroscopically deepest
penetration, should be sampled. Submit several sections
of the mucosa remote from the carcinoma, especially if
abnormal, including the lateral wall(s), dome, and trigone.
Submit one section of ureteral margin, unless sub-
mitted separately as frozen section specimens, and one
section of urethral margin. If a long segment of the ure-
ter(s) is present, then additional sections from the mid-
portion may be necessary, as urothelial cancer often is
multifocal. For additional information see: ftp://ftp.cap.
org/cancerprotocols/Blad03_p.pdf.
Appendix no. 2
Lymph nodes and distant spread
The regional lymph nodes are the nodes of the pelvis,
which essentially are the pelvic nodes below the bifur-
cation of the common iliac arteries. The significance of
the regional lymph-node metastasis in staging bladder
cancer lies in the number and size, not in whether me-
tastasis is unilateral or bilateral. One of the major prog-
nostic determinants of ultimate cure is whether the tumor
is confined to the bladder, and a major adverse prognostic
feature is the presence of any lymph-node metastasis.
Regional lymph nodes include: hypo-gastric, obtura-
tor, iliac (internal, external, not otherwise specified), peri-
vesical, pelvic (not otherwise specified), sacral (lateral,
sacral promontory), pre-sacral. The common iliac nodes
are considered sites of distant metastasis and should be
coded as M1.
It is recommended that the number of lymph nodes
submitted by the urologist should be reported. All the
nodes should be widely sampled and evaluated. In par-
ticular, submit one section from each grossly positive
lymph node. All other lymph nodes should be entirely
submitted, as presence of nodal disease may be used as an
108
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indication for adjuvant therapy. Lymph nodes may also be
grossly or microscopically detected in the perivesical fat.
In case of positive node(s), the size must be reported in
order to fulfill tumor node metastasis requirements for
staging [10] (Table 7). Distant spread is most commonly
to liver, bone, lung, and lymph nodes.
Appendix no. 3
Sampling criteria for the definition of T4
In the male, the bladder adjoins the rectum and semi-
nal vesicle posteriorly, the prostate inferiorly, and the
pubis and peritoneum anteriorly. In the female, the va-
gina is located posteriorly, and the uterus is located su-
periorly.
As far as the prostate and prostatic urethra are con-
cerned, prostatic urethral involvement should be carefully
investigated in cystectomy specimens [24, 25, 26] (Ta-
ble 8). In particular, sections should include the prostatic
urethra, including at the margin and with the surrounding
prostatic parenchyma. Representative sections of the pe-
ripheral zone, central zone, and seminal vesicles should
be included. It must be noted that there is a higher inci-
dence of prostatic adenocarcinoma in cystoprostatectomy
specimens of bladder carcinoma. Close gross examination
may help target sampling of selective abnormal-appearing
areas.
As far as other tissues are concerned, the following is
recommended: submit one or more sections of uterus as
indicated and one or more sections of vagina, seminal
vesicles, and other organs as indicated. If the tumor
grossly appears to invade the prostate, uterus, or vagina,
sections should be targeted, such that the relationship of
the infiltrating tumor in the bladder wall and the adjacent
viscera is clearly demonstrable.
Table 8 Practice parameters
for handling and reporting
bladder, ureter, and renal pelvis
specimens (checklist). TURB
transurethral resections of the
bladder, CIS carcinoma in situ,
PIN prostatic intraepithelial
neoplasia, WHO World Health
Organization, TNM/AJCC Tu-
mor Node Metastasis/American
Joint Committee on Cancer
I. General information
Pertinent clinical information: name, medical record number, data, referring physician, relevant
clinical history past and present
II. Gross description
Fresh or fixed specimen
Nature of the specimens: biopsy, chips (TURB), partial cystectomy, radical cystectomy, cysto
prostatectomy, “en bloc” resection, nephroureterectomy, ureterectomy
Total weight of resected tissue fragments (TURB); three dimensional measurements of recognizable
anatomic structures and tumors or other recognizable lesions
Site of involvement, gross fat extension
III. Diagnostic and prognostic information
Histological tumor type: urothelial, squamous, adenocarcinoma, other
Tumor grade: use current grading schemes (WHO 2004, WHO 1973, or both)
Extent of tumor in bladder (degree of invasion)*
No invasion
Invasion of the suburothelial connective tissue, muscularis propria, perivesical tissue
Presence or absence of lymphatic/vascular invasion
Tumor arising in a diverticulum (state whether muscularis propria is present)
Intraepithelial abnormalities (dysplasia, CIS)
Report focality or multifocality
Report presence of pagetoid spread of CIS (this finding is not dysplasia)
Extent of tumor in organs attached to the bladder
Prostate: direct extension to the prostate, involvement of prostatic urethra, involvement of prostatic
ducts with or without stromal involvement
Ureter, renal pelvis, and urethra: report any dysplastic/neoplastic change of the mucosa, and report
any invasion into adjacent suburothelial connective tissue or muscularis propria
Seminal vesicles: report spread of carcinoma in these organs either through epithelium or by direct
extension of an infiltrative tumor
Vagina/uterus: report direct extension or metastasis to either organ
Surgical margins: report status of ureteral/urethral margins. Report perivesical margin involvement
Report important associated conditions such PIN and adenocarcinoma of the prostate
Lymph nodes: report presence or absence of metastasis. If metastasis are present state number and
size of the largest one (<2.0 cm, 2.1 to 5 cm, >5 cm)
IV. Features considered optional in the final report
Invasion of the muscularis mucosa, if present; T1 substaging with micrometer, or just focal/wide
suburothelial connective tissue invasion
Genetic abnormalities
Cytometric examination
Morphometric examination
p53, ki-67
Other immunohistochemical markers
Stage: use TNM/AJCC 2002 revision (T1–T4, N, and M)
* Immunohistochemistry may be useful in selected cases using either cytokeratin for suburothelial
connective tissue invasion or vascular endothelial markers for vascular invasion
109
Page 7
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  • Source
    • "After each of two passes, two smears were stained for Giemsa and two for Papanicolaou. After FNAs and CBs were performed, the surgical specimen was processed according to the guidelines of the Uropathology Working Group (European Society of Pathology) [9] and the European Working Group of Uropathology of the European Association of Urology. All samples were evaluated by five pathologists blinded for the definitive diagnosis and in an independent manner. "
    [Show abstract] [Hide abstract] ABSTRACT: PURPOSE: Non-diagnostic results still hinder the routine use of core biopsy (CB) and fine needle aspiration (FNA) in the diagnostic process of renal tumours. Furthermore, substantial interobserver variability has been reported. We assessed the added value of combining the results of CB and FNA by five pathologists in the ex vivo diagnosis of renal mass. METHODS: Two ex vivo core biopsies were taken followed by two FNA passes from extirpated tumours. All samples were evaluated by five blinded pathologists. A consensus diagnosis of the surgical specimen was the index for comparison. For each pathologist, the number of non-diagnostic (non-conclusive or undetermined biology and failed biopsies), correct and incorrect scored cases of each technique was assessed. When a non-diagnostic CB or FNA had a correct diagnostic counterpart, this was considered as of added value. RESULTS: Of the 57 assessed tumours, 53 were malignant. CB was non-diagnostic in 4-10 cases (7-17.5%). FNA established the correct diagnosis in 1-7 of these cases. FNA was non-diagnostic in 2-6 cases (3.5-10.5%), and the counterpart CB established the correct diagnosis in 1-6 of these cases. For the 5 pathologists, accuracy of CB and FNA varied between 82.5-93% and 89.5-96.5%, respectively. Combination of both types of biopsy resulted in 55-57 correct results (accuracy 96.5-100%), i.e., an increase in accuracy of 3.5-14%. CONCLUSION: Combining the result of CB and FNA in renal mass biopsy leads to a higher diagnostic accuracy. Recommendations on which technique used should be adapted to local expertise and logistic possibilities.
    Full-text · Article · May 2011 · World Journal of Urology
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Bladder cancer, one of the most frequently diagnosed cancers, is a significant source of morbidity and mortality throughout the world. According to the American Cancer Society (2005), approximately 63,210 new cases will be diagnosed in the United States and bladder cancer will account for nearly 13,180 deaths. The current standard for detection of bladder cancer relies on cystoscopy, an invasive procedure, and cytology. Cytology has a high specificity, but lacks sensitivity in detection of low-grade tumors, as well as requires a trained pathologist for review. Because current diagnostic tools are less than optimal and because bladder cancer has a high rate of recurrence and long term monitoring is a necessity, a better diagnostic tool is needed. There is now a great interest in researching urine markers for bladder cancer. Our lab previously identified six nuclear structural proteins (BLCA 1-6) that are specifically expressed in bladder cancer tissue. The nuclear matrix is the support scaffold of the cell nucleus. This structure has a variety of functions, many of which have implications in cancer progression.The purpose of this dissertation is to examine changes in nuclear structural proteins. The hypothesis we propose is that changes in structural elements of the nucleus are involved in the progression of bladder cancer and can be developed into markers of this disease. Specifically this study had three goals. 1) to determine if BLCA-1 could be developed into a biomarker of bladder cancer, 2) to clone the gene encoding BLCA-1, and 3) to examine functional aspects of BLCA-4. A urine-based immunoassay was developed that can detect BLCA-1 in patients with bladder cancer with a specificity of 87% and sensitivity of 80%. Furthermore, this protein can be detected in serum of individuals with bladder cancer and may associate with the stage of disease. We also demonstrated that BLCA-4 can confer a growth advantage to cells over-expressing this protein. Over-expression of BLCA-4 led to many gene expression changes. BLCA-4 may play a role in bladder cancer pathobiology by altering genes that enhance proliferation and invasion, maintain blood flow for tumor cell survival, or enhance angiogenesis. Finally, we have been successful in cloning part of the cDNA that encodes for BLCA-1 and it appears to have a close homology to a novel metastasis related gene.In summary, this project has demonstrated that bladder cancer specific nuclear matrix proteins can be developed into markers of the disease and may play a functional role in bladder cancer pathobiology.
    Preview · Article · Jul 2005
  • No preview · Article · Sep 2008 · The Journal of urology
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