Download PowerPoint Slides English Text Spanish Translation Solid Tumors

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Solid Tumors: Diagnosis and
Staging
English Text
Solid Tumors: Diagnosing and Staging
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Professional Oncology Education
Solid Tumors: Diagnosing and Staging
Time: 23:29
Maura Polansky, MS, PA-C
Program Director
Physician Assistant Education
The University of Texas MD Anderson Cancer
Center
Hello, I am Maura Polansky at the University of
Texas MD Anderson Cancer Center. I am a
Physician Assistant in the Department of
Gastrointestinal Medical Oncology and the Program
Director for Physician Assistant Education.
Spanish Translation
Tumores sólidos: diagnóstico y estadificación
Transcripción del video
Educación Oncológica Profesional
Tumores sólidos: diagnóstico y estadificación
Duración: 23:29
Maura Polansky, MS, PA-C
Directora del programa
Educación para Asistentes Médicos
MD Anderson Cancer Center de la Universidad de
Texas
Hola, mi nombre es Maura Polansky y trabajo en el
MD Anderson Cancer Center de la Universidad de
Texas. Soy Asistente Médica del Departamento de
Oncología Gastrointestinal y Directora del Programa
de Educación para Asistentes Médicos.
Solid Tumors:
Diagnosis and Staging
Maura Polansky, MS, PA-C
Program Director
Physician Assistant Education
1
Solid Tumors: Diagnosis and
Staging
Objectives
Upon completion of this lesson, participants will be
able to:
•
•
•
•
Hoy me referiré al diagnóstico y la estadificación de
los tumores sólidos. Nuestro objetivo es hablar
sobre estos tumores, su diagnóstico y
estadificación, cómo accedemos al sitio principal de
la enfermedad, y cómo determinamos este sitio
cuando no es visible en el momento de su
presentación.
Patients present with malignancy in various different
clinical scenarios. At times, they are diagnosed
simply based on a screening physical exam or
screening test. Other times, patients come in with
particular physical findings or symptoms that
ultimately lead to the diagnosis of cancer. And
occasionally cancer is found as an incidental finding
when a test is performed for another reason, such
as a patient who may come in after a motor vehicle
accident and have a CAT scan. The clinical
presentation may be related to the primary site of
disease but, when metastatic disease is present,
sometimes this is what leads to the initial evaluation.
Los pacientes se presentan con condiciones
malignas en diferentes condiciones clínicas. A
veces su diagnóstico se basa sólo en un examen
físico o un examen preventivo. En otros casos, los
pacientes concurren con hallazgos físicos o
síntomas particulares que conducen a un
diagnóstico de cáncer. En ocasiones, el cáncer es
un hallazgo incidental al realizarse una prueba por
otra razón, por ejemplo, una tomografía en un
paciente víctima de un accidente de tránsito. La
presentación clínica puede relacionarse con el sitio
principal de la enfermedad, pero si existe
enfermedad metastásica, a veces es esto lo que
lleva a la evaluación inicial.
Discuss how solid tumors are diagnosed
Determine means of accessing primary tumors
Discuss how the primary site of disease is determined
Consider other factors in cancer staging
Solid Tumors: Diagnosis and
Staging
Initial Presentation
• Suspicion of cancer based on:
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–
–
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Today, I will be covering the diagnosis and staging
of solid tumors. Our objectives today are to discuss
solid tumors, how they are diagnosed and staged,
how we access the primary site of disease, and how
we determine the primary site of disease when it is
not apparent at the time of presentation.
Findings on routine screening
History
Physical exam
Incidental findings on diagnostic test for other
purpose
• Clinical presentation may be related to primary
tumor or metastatic disease
2
Solid Tumors: Diagnosis and
Staging
Initial Diagnosis
• Cancer is a diagnosis made by pathology:
– Biopsy typically required for cancer diagnosis
– Some exceptions exist including hepatoma
• Tissue sampling should be obtained early in the
evaluation of a patient with suspected malignancy
• Tissue can be obtained by various mechanisms
• Evaluation of tissue should distinguish malignant
vs. benign
Solid Tumors: Diagnosis and
Staging
Pathology vs. Cytology
• Cytology allows for less invasive
acquisition of cells by aspiration
of fluid and evaluation of cells
within fluid
The initial diagnosis of cancer is made based on
pathology. In almost all situations a biopsy is
required in order to confirm malignancy. There are
very rare situations in which a patient has a very
defined clinical presentation, risk factors, laboratory
studies, or imaging studies supporting the
diagnosis, and pathology is not required, such as in
hepatocellular carcinoma. These are certainly the
exception and not the rule. Otherwise, biopsy is
really required. Tissue sampling can be obtained,
and should be obtained, fairly early in the evaluation
of patients with suspected malignancy. It can be
obtained from a variety of different mechanisms that
[we] will be discussing. And the most important first
determination is whether or not the patient has a
malignancy versus a benign process.
El diagnóstico inicial de cáncer se basa en la
patología. En casi todos los casos se requiere de
una biopsia para confirmar la condición maligna.
Hay situaciones muy poco frecuentes en las cuales
un paciente tiene una presentación clínica muy
definida, factores de riesgo, estudios de laboratorio
o estudios de imágenes que respaldan el
diagnóstico, y no se requiere de la patología, como
en un carcinoma hepatocelular; estas son la
excepción y no la regla. De lo contrario, se requiere
de una biopsia. En los pacientes en los que se
sospecha una condición maligna, pueden y deben
obtenerse muestras de tejido utilizando varios
mecanismos sobre los cuales hablaremos.
Inicialmente, lo más importante es determinar si el
proceso del paciente es maligno o benigno.
Cytology allows for typically a less invasive
acquisition of cancer cells by the aspiration of fluids
and the evaluation of the cells within the fluid. This
is in contrast to a pathologic sampling in which
actual tissue is obtained either through a core
biopsy, needle biopsy, surgical biopsy, or even an
excisional biopsy.
La citología permite obtener células cancerosas de
manera menos invasiva mediante la aspiración de
líquidos y la evaluación de sus células. Esto se
contrapone a la muestra patológica, en la cual el
tejido se obtiene mediante una biopsia por punción
con aguja fina o gruesa, una biopsia quirúrgica, o
incluso una biopsia por escisión.
Cytology slide - pelvic washings
• Pathologic sampling allows for
more tissue to be obtained by core
needle biopsy, surgical biopsy or
excisional biopsy
Surgical pathology slide colon adenocarcinoma
3
Solid Tumors: Diagnosis and
Staging
Cytology
• Evaluation of cells within fluid
• Examples:
–
–
–
–
Aspiration of a tumor
Abnormal fluid collection (pleural or ascitic)
Normal fluid analysis (urine, CSF)
Washings (bronchial, peritoneal, bladder)
Solid Tumors: Diagnosis and
Staging
Pathology
• Radiographic-guided biopsy
(such as lung biopsy by
CT- guidance pictured here)
• Other means include:
– Endoscopic
(e.g. bronchoscopy, colonoscopy)
– Directed by clinical exam for palpable lesions
– Random (such as in colon or esophagus when
dysplasia has been diagnosed or suspected)
– Surgical
With cytology, the cells within the fluid are
evaluated. This fluid can be obtained by aspirating a
tumor, such as in fine needle aspiration; the removal
and analysis of an abnormal fluid collection, such as
pleural fluid or ascitic fluid: review and analysis of
normal fluid, such as urine or CSF: or with washings
in which saline is instilled into a cavity and aspirated
for review, such as with the bladder or the lung.
Con la citología, se evalúan las células del líquido.
Este líquido puede obtenerse mediante la
aspiración de un tumor, por ejemplo con una aguja
fina; la remoción y el análisis de un líquido anormal,
como el líquido pleural o ascítico; el análisis de
líquido normal, como orina o líquido
cefalorraquídeo; o con lavados con solución salina
infundida en una cavidad y aspirada para su
evaluación, como en la vejiga o el pulmón.
Pathology sampling can be obtained from
radiographic biopsy. In this case, you see a needle
that has been set into the chest cavity by means of
a CT scan to obtain a sampling of a lung nodule.
Other means include endoscopic biopsies, a
directed biopsy for a lesion that can be palpable on
a physical exam. Random biopsies are sometimes
obtained when a patient has known or suspected
dysplasia, such as an endoscopic biopsy. And at
times a surgical biopsy may be necessary.
La muestra patológica puede obtenerse mediante
una biopsia radiológica. En este caso, se observa
una aguja insertada en la cavidad torácica mediante
una tomografía para obtener una muestra de un
nódulo pulmonar. Otros medios son las biopsias
endoscópicas, una biopsia dirigida por una lesión
que pueda palparse en un examen físico. A veces
se obtienen biopsias aleatorias cuando un paciente
tiene displasia conocida o posible, como una
biopsia endoscópica, y a veces puede ser necesaria
una biopsia quirúrgica.
4
Solid Tumors: Diagnosis and
Staging
Information Obtained by Tissue
• Cytology: Based on cellular morphology
– May distinguish malignancy vs. benign disease
– Limited samples may limit further classification
• Pathology: Based on tissue morphology
– Further classification may be determined
– Determination of invasiveness
– Evaluation of malignant tissue in relationship
to normal tissue
Solid Tumors: Diagnosis and
Staging
Light Microscopy with H and E Staining
• Typically will distinguish major histological types
of malignancy
With cytology, we are able to find out about the
cellular morphology and primarily this can
distinguish malignancy versus benign disease. The
sampling is limited and, therefore, further
subclassification may or may not be possible. When
tissue is obtained through a pathologic sampling, we
can learn more about the tissue morphology and
typically further classification and subclassifications
can be made. Determination of the invasiveness of
the tumor into surrounding tissue can also be
obtained when a pathologic biopsy is obtained.
Con la citología, podemos averiguar sobre la
morfología celular y esto puede distinguir las
enfermedades malignas de las benignas. El
muestreo es limitado y, por lo tanto, una mayor
subclasificación puede o no ser posible. Cuando el
tejido se obtiene mediante una muestra patológica,
podemos saber más sobre la morfología del tejido y
se puede hacer una mayor clasificación y
subclasificación. La determinación de la invasividad
del tumor en el tejido circundante puede también
obtenerse con una biopsia patológica.
Light microscopy with H and E staining can typically
determine the major different subtypes of
malignancy and additional subtypes can be
determined with additional staining or certainly
suggest a particular subtype.
La microscopía óptica con tinción H y E permite
determinar los distintos subtipos principales de las
condiciones malignas, y los otros subtipos pueden
determinarse con tinción adicional o se puede
indicar un subtipo particular.
• May suggest subtypes which may be confirmed
by immunohistochemical staining
5
Solid Tumors: Diagnosis and
Staging
Types of Malignancies
Adenocarcinoma
Carcinoma
Squamous cell
Melanoma
Neoplasm
Lymphoma
Sarcoma
Neuroendocrine
These are the some of the major classifications of
cancer. The patient who has a neoplasm [that] can
be subdivided into a carcinoma or one of many
other types of tumor such as melanoma or sarcoma.
Carcinomas are then subdivided into a number of
different additional classifications primarily being
adenocarcinoma and squamous cell carcinoma, but
several others also exist.
Estas son algunas de las principales clasificaciones
del cáncer. El neoplasma de un paciente puede
subdividirse en un carcinoma o uno de otros varios
tipos de tumores, como melanoma o sarcoma. Los
carcinomas se subdividen en varias otras
clasificaciones adicionales, primariamente
adenocarcinoma y carcinoma de células
escamosas, pero existen otros.
When a patient comes in with a diagnosis of
malignancy or has a tumor present, one has to
consider whether, in fact, this is the primary site of
disease or it could represent a metastasis from
another site of disease. The clinician will consider
the clinical presentation of the patient, that is, signs,
symptoms, risk factors, the location and number of
tumors within that site, and the typical pattern of
metastatic spread for a particular malignancy.
Biopsies are usually obtained from the most
accessible site of disease, trying to reduce the risk
to the patient while also obtaining a good diagnostic
yield. And at times, site is determined based on
indications for treatment. That is, if it is suspected
that the patient has metastatic disease, then the
metastasis may be more appropriate to biopsy
because that not only confirms the diagnosis, but
helps with the actual staging of the patient.
Cuando un paciente llega con un diagnóstico
maligno o presenta un tumor, debe considerarse si
éeste es el principal sitio de la enfermedad o si
puede ser una metástasis de otro sitio. El clínico
analizará la presentación clínica del paciente, es
decir, las señales, los síntomas, los factores de
riesgo, la ubicación y la cantidad de tumores en ese
sitio, así como el patrón típico de diseminación
metastásica, para hallar una malignidad particular.
Las biopsias suelen obtenerse del sitio más
accesible de la enfermedad, para intentar reducir el
riesgo para el paciente y obtener un buen producto
para el diagnóstico. En ocasiones, la determinación
del sitio se basa en indicaciones del tratamiento. Es
decir, si se sospecha que el paciente tiene una
enfermedad metastásica, la metástasis puede ser
más adecuada para la biopsia ya que no sólo
confirma el diagnóstico sino que contribuye a la
estadificación del paciente.
Hepatocellular
Germ cell
Thyroid
CNS tumors
Renal cell
Other (mixed, signet, papillary)
Solid Tumors: Diagnosis and
Staging
Determining Primary vs. Metastatic Site
• Consideration of:
– Clinical presentation
– Location and number of tumor(s)
– Pattern of metastatic spread
• Biopsy performed on:
– Most accessible site
– Site most likely to yield diagnostic results
– Site most likely to influence treatment
6
Solid Tumors: Diagnosis and
Staging
Occult Primary
• Occult-metastatic cancer with primary site
not apparent
• Unknown primary-metastatic cancer when primary
site is undetectable after an appropriate evaluation
– Most commonly epithelial malignancies (carcinomas)
– Typically excludes lymphoma, melanoma, and sarcoma
– Evaluation strategies have been developed to guide an
appropriate evaluation for identifying the primary site
Solid Tumors: Diagnosis and
Staging
Types of Malignancies
Adenocarcinoma
Carcinoma
Squamous cell
Melanoma
Neoplasm
Lymphoma
Sarcoma
Neuroendocrine
Hepatocellular
Germ cell
Thyroid
CNS tumors
Renal cell
For patients who come in with metastatic disease, at
times the primary site of disease is not apparent at
initial presentation. This is called an occult primary.
This is to be distinguished from an unknown primary
in which the patient has been appropriately and
thoroughly evaluated and the primary site can still
not be determined. When patients have lymphomas,
melanomas, sarcomas, although the primary site of
disease may not be determined, the patient has a
clear established diagnosis and treatment can be
tailored to that diagnosis. However, when a patient
has a more broad classification of tumor, such as
carcinoma or simply a neoplasm, then it can be
much more helpful in guiding therapy if a particular
primary site can be determined. And there are
known strategies for making the determination
about what test should be ordered in this situation.
Again, as we look back at the major
subclassifications, when we are talking about occult
or unknown primaries, we are typically talking about
the various types of carcinoma, most commonly
adeno- [or] squamous cell carcinoma,
neuroendocrine tumors, and some of the other
tumor types. And occasionally patients simply have
a neoplasm and further calcification cannot be
obtained because of either limited tissue or the
amount of differentiation being so poor.
En los pacientes con enfermedad metastásica, el
sitio principal de la enfermedad puede no ser visible
en la presentación inicial. Esto se denomina tumor
primario oculto, y debe distinguirse de un tumor
primario desconocido, en cuyo caso el paciente ha
sido evaluado de manera exhaustiva y el sitio
principal no puede determinarse. Cuando los
pacientes presentan linfomas, melanomas o
sarcomas, si bien no puede determinarse el sitio
principal de la enfermedad, el paciente tiene un
diagnóstico claro establecido y el tratamiento puede
adaptarse a dicho diagnóstico. Sin embargo,
cuando un paciente tiene un tumor de clasificación
más amplia, como un carcinoma o un neoplasma,
determinar un sitio principal particular puede
resultar más útil para orientar la terapia. Existen
estrategias para determinar qué prueba solicitar en
esta situación.
Si observamos las subclasificaciones principales,
cuando hablamos de tumores primarios ocultos o
desconocidos, normalmente nos referimos a
diversos tipos de carcinomas, comúnmente
adenocarcinomas o carcinomas de células
escamosas, tumores neuroendócrinos y otros tipos.
En ocasiones, los pacientes simplemente tienen un
neoplasma y no se puede obtener una clasificación
adicional porque el tejido es limitado o hay escasa
diferenciación.
Other (mixed, signet, papillary)
7
Solid Tumors: Diagnosis and
Staging
Adenocarcinoma
• Breast
• Prostate
• GI
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If a patient is known to have a metastatic lesion that
is an adenocarcinoma, the clinician should consider
the various different types of primary sites of
adenocarcinoma. These include breast, prostate,
most sites within the GI tract, ovarian, lung, and
endometrial cancer.
Si se sabe que un paciente tiene una lesión
metastásica clasificada como adenocarcinoma, el
clínico debe tener en cuenta los sitios principales
del adenocarcinoma: mamas, próstata, casi todos
los sitios del cáncer del tracto digestivo, ovario,
pulmón y endometrio.
Alternatively, if the patient is known to have a
squamous cell carcinoma, consideration still of lung
cancer, but of head and neck cancers, proximal
esophagus, anus, the genitourinary tract should be
considered. Although skin cancers are often
squamous cell carcinoma, these rarely metastasize
and, therefore, would not be a serious
consideration.
Si se sabe que el paciente tiene un carcinoma de
células escamosas, debe tenerse en cuenta el
cáncer de pulmón, pero también los cánceres de
cabeza y cuello, esófago próximo, ano y tracto
genitourinario. Aunque los cánceres de piel a
menudo son carcinomas de células escamosas,
rara vez producen metástasis y no deben ser un
factor de consideración grave.
Colorectal
Pancreas
Distal esophagus
Gallbladder
Cholangiocarcinoma
• Ovary
• Lung
• Endometrium
Solid Tumors: Diagnosis and
Staging
Squamous Cell Carcinoma
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•
•
•
•
•
Head and neck
Lung
Proximal esophagus
Anus
Genitourinary tract
(Skin)
8
Solid Tumors: Diagnosis and
Staging
Neuroendocrine
•
•
•
•
Neuroendocrine tumors typically occur within the GI
tract either the large or small bowel or pancreas or
within the lungs. So these would be sites for
consideration.
Los tumores neuroendócrinos normalmente ocurren
en el tubo digestivo, el intestino delgado o grueso,
el páncreas, o los pulmones, y estos son los sitios a
tener en cuenta.
If a patient is simply found to have a poorly
differentiated carcinoma and further
subclassification cannot be performed, then these
various different subtypes have to be considered
with all the different primary sites that may be the
culprit.
Si a un paciente se le encuentra un carcinoma
escasamente diferenciado y no puede asignarse
una mayor subclasificación, estos distintos subtipos
deben considerarse con los distintos sitios
principales responsables.
Lung
Stomach
Pancreas
Small bowel
Solid Tumors: Diagnosis and
Staging
Poorly Differentiated Carcinoma
• Diagnoses to consider:
-
Adenocarcinomas
Squamous cell carcinomas
Neuroendocrine carcinomas
Hepatocellular carcinoma
Thyroid carcinoma
Renal cell
9
Solid Tumors: Diagnosis and
Staging
Poorly Differentiated Neoplasm
And similarly, on rare occasions, we see a patient
who simply has a poorly differentiated neoplasm
and virtually all cancer types have to be considered.
En situaciones poco comunes, vemos a un paciente
con un simple neoplasma con poca diferenciación y
hay que tener en cuenta casi todos los tipos de
cáncer.
Immunohistochemical staining can help in the
classification of tumors and can provide some
further information about possible primary sites.
However, a battery of tests is not recommended.
This not only raises the cost, but can provide simply
a list of positive staining that really does not help in
making the determination of [the] primary site.
Instead, when there is consideration of various sites
by the clinical presentation, a stain may help to
sway the likelihood of it being one cancer versus
another. For example, if the patient has a tumor in
the liver and it is biopsied, trying to determine
whether or not this is an adenocarcinoma versus a
hepatocellular carcinoma can be aided by looking at
the pattern of staining. Similarly mucinous
adenocarcinomas typically occur either in the GI
tract or in the ovarian [speaker indented to say
ovary], and a pattern of staining is usually quite
different for these two sites of disease.
La tinción inmunohistoquímica puede ayudar a
clasificar los tumores y brindar más información
sobre los posibles sitios principales. No se
recomienda hacer una batería de análisis. Esto no
sólo aumenta el costo, sino que puede proveer una
simple lista de tinción positiva que no ayuda mucho
para determinar el sitio principal. En su lugar,
cuando se tienen en cuenta diversos sitios en la
presentación clínica, la tinción puede ayudar a
definir un cáncer frente a otro. Por ejemplo, si el
paciente tiene un tumor en el hígado y se le hace
un biopsia, para intentar determinar si es o no un
adenocarcinoma en lugar de un carcinoma
hepatocelular puede observarse el patrón de la
tinción. De igual manera, los adenocarcinomas
mucosos suelen aparecer en el tubo digestivo o el
ovario, y el patrón de tinción generalmente es
bastante diferente en los dos sitios.
• Diagnoses to consider:
-
All types of carcinoma
Lymphoma
Melanoma
Sarcoma
Others
Solid Tumors: Diagnosis and
Staging
Immunohistochemistry
• May help in classification of tumors
• Can help clarify cases where primary site is not
readily apparent
– Universal battery is not recommended by most experts
– Specific markers may be used to distinguish subtypes
• Hepatoma vs. adenocarcinoma
• Neuroendocrine vs. adenocarcinoma vs. squamous
cell carcinoma
• Ovarian vs. GI mucin-producing adenocarcinomas
10
Solid Tumors: Diagnosis and
Staging
Immunohistochemical Staining
•
•
•
•
•
•
•
•
There are a wide variety of immunohistochemical
staining, many of them I have listed here, some of
the more common ones, such as the cytokeratin
staining, PSA, TTF1, ER/PR and so forth.
Hay una amplia variedad de tinciones
inmunohistoquímicas, muchas de los cuales he
enumerado aquí; las más comunes son la tinción
con citoqueratina, antígeno prostático específico
(PSA), factor de transcripción tiroideo (TTF1),
receptores de estrógeno y progesterona (ER/PR),
entre otros.
An example to use the cytokeratin staining might be
a patient who has a solitary lung lesion and has had
a remote history of colon cancer. This could
certainly be metastatic colon cancer or a lung
primary. And, as we looked at the pattern of staining
for cytokeratin 20 and cytokeratin 7, we typically see
a different pattern of staging --- of staining between
colon and lung cancer. And, therefore, these two
stains are routinely performed to help sway the
clinician in what the appropriate diagnosis is, which
can substantially alter the treatment of
management.
Un ejemplo para usar la tinción de citoqueratina
puede ser un paciente con una lesión solitaria de
pulmón y antecedentes remotos de cáncer de
colon. Podría, por cierto, tratarse de cáncer de
colon metastático o un tumor primario de pulmón.
En el patrón de tinción con citoqueratina 20 y
citoqueratina 7 normalmente observamos un patrón
distinto de tinción entre el cáncer de colon y el de
pulmón. Por lo tanto, estas dos tinciones se realizan
como rutina para que el clínico pueda definir el
diagnóstico adecuado, que puede alterar mucho el
tratamiento.
Cytokeratin stains
PSA, PAP
TTF 1
ER/PR
Gross cystic disease fibrous protein (GCDFP)
C-kit
Hep par
Uroplakin III (UROIII)
Solid Tumors: Diagnosis and
Staging
Example: Cytokeratin
• CK 7: lung, ovary, endometrium and breast
• CK 20: GI tract, urothelium and Merkel cells
CK pattern
Malignancy
20 +, 7 +
Urothelial, ovarian mucinous, biliary, pancreas
20 +, 7 -
Colon cancer, Merkel cell
20 -, 7 +
Lung, breast, thyroid, cervical, biliary, pancreas,
ovarian, endometrial
20 -, 7 -
HCC, renal cell, prostate, H&N, squamous cell and
small cell lung
NCCN GuidelinesTM for occult primary V.1.2010, www.nccn.org
11
Solid Tumors: Diagnosis and
Staging
Limitation of Pathology Review
• Adequate sample necessary
• Excessive testing adds to the cost and
may be misleading
• Stains are neither sensitive nor specific
• Information obtained should be considered
within the context of the hematoxylin and eosin staining
and clinical scenario
• Interpretation is dependent on experience of
pathologist and clinician
Solid Tumors: Diagnosis and
Staging
Approach After Biopsy if Primary Site is Still
Not Known
• Consideration of clinical presentation*
• Re-consideration of history
• Ensure complete physical examination
• Obtain routine labs including appropriate
tumor markers
• Order directed imaging studies and other
diagnostic studies*
• Consider consultation with pathologist
*NCCN GuidelinesTM for occult primary V.1.2010, www.nccn.org
Keep in mind that pathology can be quite helpful in
aiding in the diagnosis of a patient, but has
limitations. One is the limitations of sampling. Again,
we have talked about the limitations of cytology
versus being able to obtain more tissue. The cost
that is incurred, the more staining that is performed,
and how that can sometimes actually be misleading
with almost too much information provided. Stains
are neither 100% sensitive or specific, so again, can
simply lead to further consideration or further
evidence of one disease versus another. And really,
looking back at the H and E staining, the clinical
scenario is most important in guiding the overall
impression of the primary site of disease. And
consultation with the pathologist can be quite helpful
and this really depends on the experience of the
clinician and the pathologist.
Debe tenerse en cuenta que la patología puede ser
bastante útil para el diagnóstico de un paciente,
pero tiene limitaciones. Una de las limitaciones es el
muestreo. Ya hemos hablado sobre las limitaciones
de la citología respecto de la posibilidad de obtener
más tejido, del costo en que se incurre cuantas más
tinciones se realizan, y cómo esto puede resultar
engañoso con casi demasiada información. Las
tinciones no son 100% sensibles o específicas, por
lo cual sirven simplemente como otra consideración
o prueba para definir una enfermedad. En cuanto a
la tinción H y E, la situación clínica es la más
importante para orientar la impresión general del
sitio principal de la enfermedad. La consulta con el
patólogo puede ser útil, pero su experiencia y la del
clínico influyen en gran medida.
If, after a biopsy is obtained, the primary site is still
not determined, then reconsideration of the clinical
presentation. Is this patient at particularly high risk
of certain types of cancers based on family history
or other personal history? What about the patient’s
presenting signs and symptoms? Do they suggest a
possible site of primary disease? Are there any
laboratory studies that support one diagnosis or
another? And then imaging studies should be
performed in a thoughtful manner. That is, we don’t
order lots and lots of tests. We order those that we
feel will be appropriate given the tissue type and
TM
given the clinical scenario. The NCCN Guidelines
can be quite helpful in guiding this evaluation for
those who do not often see cancers of unknown
primary. And consideration of consulting with the
pathologist to see what additional information he or
she may be able to suggest.
Si, luego de una biopsia, no se determina aún el
sitio principal, debe volverse a considerar la
presentación clínica. ¿Tiene este paciente un riesgo
particularmente alto para ciertos tipos de cánceres
basados en los antecedentes familiares o
personales? ¿Qué sucede si el paciente presenta
síntomas? ¿Indican un posible sitio principal de la
enfermedad? ¿Existen estudios de laboratorio que
respalden un diagnóstico u otro? Los estudios de
imágenes deben realizarse de manera reflexiva. Es
decir, no se deben pedir montones de análisis.
Deben pedirse los que consideramos adecuados en
función del tipo de tejido y la situación clínica. Las
pautas de la Red Nacional Integral del Cáncer
TM
(NCCN Guidelines ) pueden resultar útiles para
orientar esta evaluación para quienes no suelen ver
cánceres de tumor primario desconocido, y debe
consultarse al patólogo para comprobar qué
información adicional puede sugerir.
12
Solid Tumors: Diagnosis and
Staging
Tumor Markers
• Substances typically found in the blood
• Role
–
–
–
–
Screening
Limited value in determining primary
Use in surveillance and identifying recurrence
Monitoring on therapy for disease response
• Limitations of tumor markers
– Sensitivity and specificity
– Affected by other factors
I mentioned tumor markers. These are substances
found in the blood and at times urine and another
normal fluid. It can --- they can be very helpful in
screening, such as with PSA for prostate cancer
and with alpha-fetoprotein for hepatocellular
carcinoma. They have a small, but limited role in
making an initial diagnosis of a primary site of
disease. They can be very helpful for surveillance
for a patient who has already completed treatment
and is felt to be in remission. If the tumor marker
rises, that may suggest recurrent disease. And they
also can be used to monitor a patient on therapy to
see if it appears that they are having an early
response or the treatment is not effective. As with
staining, tumor markers are not completely sensitive
or specific. There are many tumor markers, such as
CEA, that can be elevated in a wide variety of
malignancies. And they can occasionally be affected
by other factors, such as hepatic function or whether
a patient is a smoker.
Ya mencioné los marcadores tumorales. Son
sustancias que se encuentran en la sangre y a
veces en la orina y otros líquidos normales. Pueden
ser muy útiles para los exámenes preventivos,
como el PSA para el cáncer de próstata y la
alfafetoproteína para el carcinoma hepatocelular.
Cumplen una cierta función limitada en el
diagnóstico inicial del sitio principal de una
enfermedad. Pueden ayudar a vigilar a un paciente
que ha concluido su tratamiento y que se considera
en remisión. Si el marcador tumoral aumenta,
puede sugerir una enfermedad recurrente. También
pueden utilizarse para monitorear a un paciente
durante la terapia para determinar si existe una
respuesta temprana o si el tratamiento no es
efectivo. Al igual que la tinción, los marcadores
tumorales no son completamente sensibles o
específicos. Muchos marcadores tumorales, como
el antígeno carcinoembrionario (CEA), pueden
elevarse en varias condiciones malignas. En
ocasiones pueden verse afectados por otros
factores, como la función hepática o si el paciente
es fumador.
13
Solid Tumors: Diagnosis and
Staging
Tumor Markers
• Hormones
– HCG
– Calcitonin
– Catecholamines
• Enzymes
– PAP
– LDH
– Neuron-specific
enolase
There are a variety of different types of tumor
markers. Some are hormones, enzymes, proteins or
antigens; and a number of them have been listed
here. Many of these I am sure you are familiar with.
Hay varios y distintos marcadores tumorales.
Algunos son hormonas, enzimas, proteínas o
antígenos; y varios han sido ya enumerados. Estoy
segura de que ya conocen varios.
Tumors can be classified based on attributes of their
behavior and, therefore, a staging system has been
established to help in further guiding the process of
treatment, estimating prognosis, and are important
in clinical research so that we are sure when we are
looking at two different treatment arms that these
are patients who are similar.
Los tumores pueden clasificarse según sus
atributos de comportamiento, y se ha establecido un
sistema de estadificación para orientar el
tratamiento y estimar el pronóstico. Son importantes
para la investigación clínica, para estar seguros de
que estos pacientes dentro de dos grupos distintos
del tratamiento son similares.
• Antigens
– AFP
– CEA
• Proteins
– PSA
– CA 19-9, 125, 25.27
– CD 30, 25
Solid Tumors: Diagnosis and
Staging
Classification and Staging
• Tumors are classified based on attributes that
define its behavior
• Classifications are based on the premise that
cancers of the same site and histology share
similar outcomes
• Defining the cancer stage is important in:
– Estimating prognosis
– Guiding treatment
– Clinical research (since treatments and outcomes
should vary by stage)
14
Solid Tumors: Diagnosis and
Staging
Staging Systems
• American Joint Committee on Cancer (AJCC) is
the primary staging system for most malignancies
The American Joint Committee on Cancer is the
primary staging system used for solid tumors. It
includes both pathologic staging and clinical
staging. The most commonly used, that of the TNM
staging, looking at the tumor, the regional lymph
nodes, and metastases.
El Comité Conjunto Americano sobre el Cáncer es
el principal sistema de estadificación utilizado para
los tumores sólidos. Incluye tanto la estadificación
patológica como la clínica. El más utilizado, la
estadificación TNM, analiza el tumor, los ganglios
linfáticos regionales y las metástasis.
The tumor can be staged by different characteristics
depending on the type of tumor it is. For certain
tumors, we look at the size of the tumor, such as in
lung, breast, ovarian, or prostate cancer. Tumors
over a particular size have a higher T-staging.
El tumor puede estadificarse según distintas
características, en función del tipo de tumor. Para
ciertos tumores, se debe considerar el tamaño del
tumor, como en el cáncer de pulmón, mama, ovario
o próstata. Los tumores que exceden un tamaño
particular tienen una estadificación T más alta.
• Pathologic staging
• Clinical staging
– TNM
• Tumor
• Nodes (regional)
• Metastasis
Solid Tumors: Diagnosis and
Staging
Tumor Stage
Many tumors are staged by size such as:
•
•
•
•
Lung
Breast
Ovarian
Prostate
Lung mass on CT scan
15
Solid Tumors: Diagnosis and
Staging
Tumor Stage
Bowel and bladder cancers as well as melanomas
are staged by depth of penetration
Solid Tumors: Diagnosis and
Staging
Nodal Stage
• Nodal stage is based on:
- Number
- Location (regional)
This is in contrast to a tumor such as a tumor within
the bowel wall. This is an endoscopic ultrasound
that shows a tumor that extends throughout the
muscularis of the colon and therefore is a T3 lesion.
Similarly with bladder cancers and melanomas, the
depth of penetration is what determines the Tstaging.
Esto se contrapone a un tumor como el alojado
dentro de la pared del intestino. Esta ecografía
endoscópica muestra un tumor que se extiende por
la capa muscular del colon, una lesión T3. Con
cánceres de vejiga y melanomas, la profundidad de
penetración es lo que determina la estadificación T.
Nodal stage is related to regional lymph nodes, the
location and the number of nodes within the direct
region of the primary tumor. Keep in mind that, if the
patient has a lymph node distant from the site of
[the] primary, then this would represent metastatic
disease.
La etapa ganglionar se relaciona con los ganglios
linfáticos regionales, la ubicación y la cantidad de
ganglios en la región directa del tumor principal.
Tenga en cuenta que si el paciente tiene un ganglio
linfático lejos del sitio principal, esto representaría
una enfermedad metastásica.
• Distant lymph node involvement
is considered metastasis based
on the presumption that this is
hematologic spread
16
Solid Tumors: Diagnosis and
Staging
Nodal Stage
• Clinical evaluation of nodes can be made for tumors
when regional lymph nodes may be palpable such as:
–
–
–
–
Melanoma
Breast
Head and neck
Anal
• Physical examination of cancer patients should include
palpation of cervical, supraclavicular, axillary and
inguinal nodes to determine abnormal regional or
distant (metastatic) nodal spread
Solid Tumors: Diagnosis and
Staging
Nodes may be assessed by imaging studies such a CT, MRI or
ultrasound based on size and appearance of regional nodes
There are cases where the patient’s nodes can be
assessed by physical exam, such as if a patient has
a melanoma or breast cancer. Head and neck
cancers, for example, will drain into the neck region
and can be palpated on exam. Anal cancers have
the inguinal region as their --- one of their sites of
nodal drainage and, therefore, these areas can be
assessed and should be assessed on physical
exam of these patients. And with all patients,
examination of all the palpable nodal basins,
cervical, supraclavicular, axillary and inguinal
nodes, should be performed as part of an initial
evaluation to determine if there is regional or
metastatic nodal involvement.
Hay casos en los que los ganglios pueden
evaluarse con un examen físico, como en
melanomas o cáncer de mama. Los cánceres de
cabeza y cuello, por ejemplo, se filtran a la región
del cuello y pueden palparse en un examen. Los
cánceres de ano pueden tener la región inguinal
como uno de sus sitios de drenaje ganglionar, por lo
que estas áreas pueden y deben evaluarse en un
examen físico. Con todos los pacientes, el examen
de todas las cuencas ganglionares palpables, los
ganglios cervicales, supraclaviculares, axilares e
inguinales debe formar parte de la evaluación inicial
para determinar si hay participación ganglionar
regional o metastásica.
Additional nodes can be evaluated by CT, MRI, or
ultrasound. The size of the nodes and the
characteristic of the nodes can be determined by
the radiologist to be suggestive of that of nodal
involvement. And, if necessary, biopsy or aspiration
of that node may be necessary to determine if, in
fact, they are involved, and this would be done only
if this is going to affect the clinical management of
the patient.
Los ganglios adicionales pueden evaluarse con una
tomografía, resonancia magnética o ecografía. El
tamaño y las características de los ganglios pueden
sugerir al patólogo si hay compromiso ganglionar.
Posiblemente sea necesario hacer una biopsia o
una aspiración de ese ganglio para determinar si
está comprometido, y esto sólo se haría si afectase
la gestión clínica del paciente.
Biopsy or aspiration of nodes may be performed to confirm
involvement when this will affect treatment
17
Solid Tumors: Diagnosis and
Staging
Node Staging
• Regional nodes are most
often staged surgically,
at the time of primary
tumor resection
Nodes are most commonly identified and diagnosed
at the time of surgical resection of the primary site of
disease. And this is the most accurate and useful
information, although there are times where, in a
preoperative setting, one needs to determine if
nodal involvement is present.
Los ganglios son normalmente identificados y
diagnosticados en el momento de la resección
quirúrgica del sitio principal de la enfermedad. Esta
es la información más precisa y útil, aunque en un
contexto preoperatorio se debe determinar si hay
compromiso ganglionar.
Metastases can certainly be suspected based on
clinical examination or presenting symptoms. If a
patient has organomegaly or palpable mass, such
as an intra-abdominal mass or soft tissue tumor, this
can certainly be suggestive of metastatic disease.
Clinical evaluation and determination of what
diagnostic tests should be ordered should be
determined based on common sites of metastatic
spread for that particular tumor type. And there are
consensus guidelines regarding the appropriate
evaluation for patients when they have a particular
tumor type. Rarely, surgical evaluation is needed for
establishing the presence of metastatic disease, but
occasionally this is required or this occurs if a
patient is going to surgery.
La sospecha de metástasis puede basarse en un
examen clínico o en la presencia de síntomas. Si un
paciente tiene organomegalía o masa palpable,
como una masa intraabdominal o un tumor de tejido
blando, esto puede ser un claro indicio de una
enfermedad metastásica. La evaluación clínica y la
determinación de las pruebas de diagnóstico que
deben pedirse deben determinarse en función de
los sitios comunes de la diseminación metastásica
de ese tipo de tumor particular. Hay pautas
consensuadas sobre la evaluación adecuada de
pacientes cuando tienen un tipo de tumor particular.
Rara vez se necesita un examen quirúrgico para
establecer la presencia de una enfermedad
metastásica, pero en ocasiones se requiere u
ocurre si un paciente se somete a una intervención
quirúrgica.
• Most accurate determination
of lymph node involvement
occurs with:
– Evaluation at the time
of surgery
– Adequate lymph
node dissection
– Thorough pathologic review
Solid Tumors: Diagnosis and
Staging
Metastasis
• Suspicion of metastasis raised during physical exam
by noting organomegaly (esp. liver), intra-abdominal
masses or soft tissue tumors
• Clinical evaluation should focus on common sites
of metastasis for the specific malignancy
• Consensus guidelines and clinician assessment
of the site of primary malignancy should direct the
radiologic evaluation
• Rarely surgical evaluation is used to establish or
confirm metastatic disease
18
Solid Tumors: Diagnosis and
Staging
Common Imaging Studies for Cancer Staging
•
•
•
•
•
There are number of common imaging studies that
are used in the evaluation of cancer patients, CT,
MRI, ultrasound, PET scan, and bone scan.
Hay varios estudios de imágenes comunes
utilizados en la evaluación de pacientes con cáncer,
tomografías computadas, resonancias magnéticas,
ecografías, PET y gammagrafías óseas.
With CT scan, we obtain cross-sectional imaging
typically in the range of 3 to 5 mm, sometimes as
wide as 10 mm sections. It does require IV contrast
and GI contrast is typically used for evaluation of the
abdomen or pelvis. And there are sometimes
contraindications particularly to IV contrast if the
patient has renal impairment.
Con la tomografía computada, normalmente
obtenemos imágenes transversales de 3 a 5 mm, a
veces con cortes de 10 mm de ancho. Requiere
contraste intravenoso (IV), y se suele utilizar
contraste gastrointestinal (GI) para evaluar el
abdomen o la pelvis. A veces hay
contraindicaciones, particularmente para un
contraste IV, si el paciente tiene insuficiencia renal.
CT
MRI
Ultrasound
Bone scan
PET scan
Solid Tumors: Diagnosis and
Staging
Computed Tomography Scan
• Provides cross-sectional imaging (3-10 mm)
• Requires IV contrast which is contraindicated
in renal impairment
• GI contrast required for imaging of abdomen
and pelvis
19
Solid Tumors: Diagnosis and
Staging
CT Scan
CT scans are commonly used for evaluation of the
lung, the liver, the pancreas, the brain, and lymph
nodes, such as the example here with the lesion in
the liver seen on CAT scan.
Las tomografías computadas se utilizan
generalmente para examinar el pulmón, el hígado,
el páncreas, el cerebro y los ganglios linfáticos,
como en la lesión de hígado que se observa en esta
tomografía.
MRI uses radiofrequency signals to produce an
image. It does require being in a closed MRI
machine. Although there are open MRI machines,
these are inferior to closed machines and really play
very little role in the management and evaluation of
cancer patients. Some patients will require sedation
in order to be in a closed MRI machine.
La resonancia magnética usa señales de
radiofrecuencia para generar una imagen, y
requiere un examen en una máquina cerrada. Si
bien hay máquinas abiertas para resonancias
magnéticas, son inferiores a las cerradas y cumplen
un papel menor en la gestión y la evaluación de
pacientes con cáncer. Algunos pacientes deben ser
sedados para permanecer en una máquina cerrada
para resonancias magnéticas.
• Commonly used in imaging of:
–
–
–
–
–
Lungs
Liver
Pancreas
Brain
Lymph nodes
Hypodense lesion in the
liver consistent with
hepatic metastasis
Solid Tumors: Diagnosis and
Staging
Magnetic Resonance Imaging
• Use of radio frequency
signals to produce
an image
• Requires enclosure in
MRI machine
• Open MRI images inferior
to closed machine
20
Solid Tumors: Diagnosis and
Staging
MRI
• Useful for CNS or soft
tissue lesions
• Also used for body
imaging
• May help to distinguish
types of hepatic lesions
MRIs are particularly useful at looking at CNS
tumors and soft tissue masses. They can also be
used, however, to image all the other sites that were
mentioned with CT scan, such as brain, lung, and
liver. And they can be particularly helpful in
distinguishing certain types of tumors, different
characteristics within the tumor (such as those in
the liver). So, additional information can sometimes
be performed and obtained beyond that obtained in
the CAT scan.
Las resonancias magnéticas son útiles para
examinar tumores del sistema nervioso central y
masas de tejido blando. También pueden utilizarse
para tomar imágenes de los otros sitios
mencionados con la tomografía, como el cerebro, el
pulmón y el hígado. Pueden ayudar mucho para
distinguir ciertos tipos de tumores, y sus distintas
características (como en el hígado). Por lo tanto, a
veces es posible obtener información adicional a la
obtenida con la tomografía.
Ultrasound avoids the risk of radiation and contrast.
It can be performed percutaneously, endoscopically,
or intraoperatively.
La ecografía evita el riesgo de radiación y contraste.
Puede realizarse de manera percutánea,
endoscópica o intraoperatoria.
Choroid Plexis Papillomas
Solid Tumors: Diagnosis and
Staging
Ultrasound
• Avoids risk of radiation or contrast
• Can be performed:
– Percutaneously
– Endoscopically
– Intraoperatively
21
Solid Tumors: Diagnosis and
Staging
Ultrasound
• Help to distinguish cystic vs. solid tumors
such as hepatic lesions
It is very helpful in helping to distinguish cystic
versus solid tumors, such as in the breast or in the
ovary or liver where we often see cystic lesions and
can really provide some complementary information
beyond that of CT or MRI.
Es muy útil para ayudar a distinguir los tumores
quísticos de los sólidos, como en la mama, el ovario
o el hígado, donde vemos a menudo lesiones
quísticas, y también puede brindar información
suplementaria a la tomografía o la resonancia.
Bone scan is a nuclear medicine study in which a
patient is injected with a tracer. It identifies areas of
high bone turnover that may be malignancy
although other processes can also result in this
abnormal signaling. One of the advantages: the
entire skeleton is surveyed with a bone scan. So
this is a particularly useful test when patients have a
malignancy that commonly metastasizes to the
bone.
La gammagrafía ósea es un estudio de medicina
nuclear en el cual el paciente recibe una inyección
con trazador. Identifica áreas de recambio óseo que
pueden ser malignas, aunque otros procesos
también pueden llevar a esta señal anormal. Una de
las ventajas: la gammagrafía ósea permite explorar
todo el esqueleto. Este examen es particularmente
útil cuando los pacientes presentan una malignidad
que normalmente produce metástasis en el hueso.
• Can provide complementary information
to radiographs
Solid Tumors: Diagnosis and
Staging
Bone Scan
• Nuclear medicine study
• Detects patient injected tracer
• Identifies areas of high bone turnover
• Surveys full skeleton
22
Solid Tumors: Diagnosis and
Staging
Bone Scan
Bone scan can detect both primary sites of bone
disease as well as metastatic disease to the bone. It
is particularly helpful in osteolytic lesions and less
helpful in osteoblastic lesions.
La gammagrafía ósea puede detectar tanto la
enfermedad ósea principal como la metastásica. Es
particularmente útil para las lesiones osteolíticas y
menos útil para las osteoblásticas.
PET scan is another nuclear medicine study that
obtains physiologic images detecting positrons
emitted after injecting a patient with a tracer. FDG is
laced with a positron --- a radiotracer isotope, which
emits a positron on decay and it identifies areas of
high metabolic activity in the body that can be
malignancy. But other conditions, such as
inflammatory or infectious processes can also light
up on PET scan.
La tomografía PET es otro estudio de medicina
nuclear que obtiene imágenes fisiológicas que
detectan los positrones emitidos luego de inyectar
el trazador al paciente. A la fluorodesoxiglucosa
(FDG) se le agrega un positrón, un isótopo
radiotrazador que emite un positrón en
descomposición e identifica áreas de alta actividad
metabólica del organismo que puedan ser malignas.
Sin embargo, la tomografía PET también puede
aclarar otras condiciones, como los procesos
inflamatorios o infecciosos.
• May detect primary or metastatic bone involvement
• Most beneficial for osteolytic lesions as opposed
to osteoblastic
Multiple areas of abnormal uptake within
skeleton representing bone metastases
Solid Tumors: Diagnosis and
Staging
PET Scan
• Nuclear medicine study
• Obtains physiologic images by detecting
• Positrons emitted after injecting patients
with tracer
• Fluorodeoxyglucose (FDG) is laced with
radiotracer isotope which will emit a positron
on decay
• Identifies areas with high metabolic activity
23
Solid Tumors: Diagnosis and
Staging
PET Scan Use in Staging
• Can identify other possible
sites of disease, lymph nodes
and distance metastatic
disease
PET scan is used in staging more routinely for a
number of different cancers. It can identify possible
sites of disease including lymph node involvement
and metastatic disease and it is routinely combined
with CAT scan to give more anatomic detail to the
site of involvement.
La PET se utiliza para estadificar distintos cánceres
en forma más rutinaria. Puede identificar posibles
sitios de la enfermedad, incluido el compromiso del
ganglio linfático y la enfermedad metastásica, y se
combina periódicamente con la tomografía
computada para obtener más detalles anatómicos.
In conclusion, the diagnosis of most cancers
requires review of pathologic information obtained
from biopsy or aspiration. The determination of a
primary site of disease requires consideration of the
clinical presentation, pathologic review, and
consideration of patterns of metastatic spread.
Cancer staging is a very important step in
evaluation of patients with malignancy to estimate
prognosis; help to guide treatment
recommendations; and also in stratifying patients
who will be participating in clinical trials. This
concludes our presentation today. We hope you find
this useful and we will welcome your feedback.
En conclusión, el diagnóstico de la mayor parte de
los cánceres requiere la evaluación de la
información patológica obtenida por biopsia o
aspiración. La determinación del sitio principal de la
enfermedad requiere un análisis de la presentación
clínica, una evaluación patológica y un análisis de
los patrones de diseminación metastásica. La
estadificación del cáncer es un paso muy
importante para evaluar a pacientes con
condiciones malignas y estimar el pronóstico; para
orientar recomendaciones de tratamientos; y
también para estratificar a los pacientes que
participarán en ensayos clínicos. Esto concluye
nuestra presentación de hoy. Esperemos que les
haya resultado útil y lo invitamos a hacernos
comentarios.
• May be combined with
CT scan to provide
better delineation of
site of hypermetabolism
Abnormal retroperitoneal lymph
nodes and mass. Normal uptake
in brain and bladder.
Solid Tumors: Diagnosis and
Staging
Conclusions
• Diagnosis of most cancers requires review of
pathologic information
• Determination of a primary site of disease
requires consideration of clinical presentation,
pathology review and pattern of metastatic spread
• Cancer staging is an important step in evaluating
patient with malignancy in estimating prognosis,
establishing treatment recommendation and in
stratifying patients participating in clinical research
24