VideoTranscript Professional Oncology Education Solid ......– Some exceptions exist including hepatoma • Tissue sampling should be obtained early in the evaluation of a patient

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Solid Tumors: Diagnosing and Staging VideoTranscript

实体肿瘤：诊断与分期视频文本

Professional Oncology Education Solid Tumors: Diagnosing and Staging Time: 23:29

专业人员肿瘤教学讲座实体肿瘤：诊断与分期时间： 23:29

Maura Polansky, MS, PA-C Program Director Physician Assistant Education The University of Texas MD Anderson Cancer Center

德克萨斯大学 MD Anderson 癌症中心医生助理教育部计划主管

Maura Polansky, MS, PA-C

Solid Tumors: Diagnosis and Solid Tumors: Diagnosis and Solid Tumors: Diagnosis and Solid Tumors: Diagnosis and

Staging Staging Staging Staging

Solid Tumors: Solid Tumors:

Diagnosis and StagingDiagnosis and Staging

Maura Polansky, MS, PA-C

Program Director

Physician Assistant Education

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.

大家好，我是德克萨斯大学 MD Anderson 癌症中心的 Maura Polansky,担任胃肠道肿瘤科的医生助理兼医生助理教育部的计划主管。

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ObjectivesObjectivesObjectivesObjectives

Upon completion of this lesson, participants will be

able to:

• 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

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.

今天我要介绍的是实体肿瘤的诊断与分期。我们今天的目的是讨论实体肿瘤及其诊断与分期，如何到达肿瘤的原发部位，如果患者前来就诊时原发部位不明显，如何判断肿瘤的原发部位。



Initial PresentationInitial PresentationInitial PresentationInitial Presentation

• Suspicion of cancer based on:

– 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

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.

可以在各种的临床环境下发现患者的恶性肿瘤。有些患者单凭筛查体检或筛查测试得到诊断而有些患者出于特定体检结果或症状前来就医，并最终得到癌症的诊断。有时是因为其他原因进行某项测试而意外发现癌症。例如患者可能是因为车祸前来就医，在接受

CAT 扫描时发现癌症。临床表现可能与癌症的原发部位有关。但是出现癌症转移时，有时则是因为转移症状而导致初始评估。

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Initial DiagnosisInitial DiagnosisInitial DiagnosisInitial 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

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.

对癌症的初始诊断依据的是病理检查结果。几乎所有的情况都需要通过活检确认恶性肿瘤。在非常罕见的情况下，患者有十分明确的临床表现、风险因素、化验检查结果或成像检查结果支持诊断。此时不需要进行病理检查。这样的例子有肝细胞癌。这当然属于例外，并非常规做法。除此之外，活检必不可少。可以也应该在评估疑似恶性肿瘤患者的非常早期进行组织采样。采样方法可以采用我们将要讨论的几种不同的方式。首要考虑因素是患者是有恶性肿瘤还是良性肿瘤。



Pathology vs. CytologyPathology vs. CytologyPathology vs. CytologyPathology vs. Cytology

• Cytology allows for less invasive

acquisition of cells by aspiration

of fluid and evaluation of cells

within fluid

• Pathologic sampling allows for

more tissue to be obtained by core

needle biopsy, surgical biopsy or

excisional biopsy

Cytology slide - pelvic washings

Surgical pathology slide -

colon adenocarcinoma

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.

细胞学检查使用创伤性较小的方法来采集癌细胞，通常可以抽吸液体，然后评估液体内的细胞。。与之相反，病理学采样则通过粗针穿刺活检、细针穿刺活检、外科活检，甚至是切除式活检来取得实际的组织。

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CytologyCytologyCytologyCytology

• 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)

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.

细胞学检查会评估液体里的细胞。可以通过以下方法获得液体：穿刺肿瘤（例如细针穿刺）、切除并分析采集的异常液体（例如胸膜液或腹水）、查看和分析正常液体（例如尿液或脑脊液）或者查看抽吸体腔内生理盐水冲洗液（例如膀胱或肺冲洗液）。



PathologyPathologyPathologyPathology

• 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

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.

病理检查样本可以通过放射成像活检获得。在这个案例中，可以看见一根针在 CT 扫描的引导下插入了胸腔，对肺结节进行采样。其他方式包括内窥镜活检、对体检可以触及的病灶进行的引导穿刺活检。在患者已知或疑似有异常增生时，有时可以使用随机活检，例如内窥镜活检。有时可能有必要进行手术活检。

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Information Obtained by TissueInformation Obtained by TissueInformation Obtained by TissueInformation 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

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.

使用细胞学检查，我们可以查明细胞形态，这主要可以用来区分恶性和良性疾病。由于采样受限，所以可能无法做进一步的细分。如果是通过病理学采样获得组织，则可以更多了解组织形态，一般还可以进一步分型和细分。还可以通过病理学活检确定肿瘤对周围组织的浸润性。



• Typically will distinguish major histological types

of malignancy

• May suggest subtypes which may be confirmed

by immunohistochemical staining

Light Microscopy with H and E StainingLight Microscopy with H and E StainingLight Microscopy with H and E StainingLight Microscopy with H and E Staining

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.

通过 H 和 E 染色的光学显微镜检查，通常可以判定恶性疾病的主要亚型。还可以使用其他染色方法来判定或者提示某种亚型。

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Types of MalignanciesTypes of MalignanciesTypes of MalignanciesTypes of Malignancies

Neoplasm

Melanoma

Lymphoma

Sarcoma

Germ cell

CNS tumors

Carcinoma

Adenocarcinoma

Squamous cell

Neuroendocrine

Hepatocellular

Thyroid

Renal cell

Other (mixed, signet, papillary)

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.

这些是癌症的部分主要分型。患者的赘瘤可以细分为癌症或许多其他肿瘤中的一种，例如黑色素瘤或肉瘤。接下来癌症可以被细分为一系列其他不同的分型，主要是腺癌和鳞细胞癌，但也存在其他几种类型。



Determining Primary vs. Metastatic SiteDetermining Primary vs. Metastatic SiteDetermining Primary vs. Metastatic SiteDetermining 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

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.

当患者被诊断患有恶性疾病或者出现肿瘤而前来就诊时，我们必须考虑这是否就是疾病的原发部位，还是其他部位癌症的转移病灶。临床医生要考虑患者的临床表现，即患者的体征、症状、风险因素、患病部位和患病部位内的肿瘤数目，以及特定恶性疾病的惯常转移模式。一般在最容易操作的患病部位做活检，以便尽量减少给患者造成的风险，同时要获得可靠的诊断结果。有时候是依据治疗指征来决定活检部位。也就是说，如果怀疑患者有转移，则转移病灶可能更适用于活检，这样不仅可以确认诊断结果，而且还有助于对患者进行分期。

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Occult PrimaryOccult PrimaryOccult PrimaryOccult 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

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.

对于就诊时已有转移的患者，有时原发部位的疾病在初诊时并不明显。这称为隐匿原发病灶。这是与不明原发病灶相区分。有不明原发病灶的患者，在接受了适当的全面评估之后，可能仍无法判定原发病灶。如果患者患有淋巴瘤、黑色素瘤、肉瘤，即使未能判定原发病灶，患者仍能得到确诊，并根据诊断来定制治疗。但是，如果患者的肿瘤属于更为广泛的分型，比如癌症或者仅仅是赘瘤，则判定具体的原发部位会对治疗方法起到更大的指导作用。有已知策略来指导在这种情况下应该进行什么样的检测。



Types of MalignanciesTypes of MalignanciesTypes of MalignanciesTypes of Malignancies

Adenocarcinoma

Squamous cell

Neuroendocrine

Hepatocellular

Thyroid

Renal cell

Other (mixed, signet, papillary)

Neoplasm

Melanoma

Lymphoma

Sarcoma

Germ cell

CNS tumors

Carcinoma

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.

让我们回顾一下主要的细分类型。我们谈论隐匿或不明原发病灶时，通常是指癌症的不同类型。最常见的是腺癌或鳞状细胞癌、神经内分泌肿瘤和某些其他肿瘤类型。有时患者只有赘瘤诊断，因为组织样品有限或者分化极度不良而无法进一步分型。

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AdenocarcinomaAdenocarcinomaAdenocarcinomaAdenocarcinoma

• Breast

• Prostate

• GI

– Colorectal

– Pancreas

– Distal esophagus

– Gallbladder

– Cholangiocarcinoma

• Ovary

• Lung

• Endometrium

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.

如果已知患者有属于腺癌的转移病灶，临床医生应该考虑各种不同类型的腺癌原发部位，包括乳腺癌、前列腺癌、胃肠道的多数部位癌症、卵巢癌、肺癌和子宫内膜癌。



Squamous Cell CarcinomaSquamous Cell CarcinomaSquamous Cell CarcinomaSquamous Cell Carcinoma

• Head and neck

• Lung

• Proximal esophagus

• Anus

• Genitourinary tract

• (Skin)

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.

或者，如果已知患者有鳞状细胞癌，则仍需考虑肺癌，但还要考虑头颈癌、上段食道癌、肛门癌、生殖泌尿道癌。尽管皮肤癌常常是鳞状细胞癌，但这类鳞状细胞癌极少转移，所以无需着重考虑皮肤癌。

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NeuroendocrineNeuroendocrineNeuroendocrineNeuroendocrine

• Lung

• Stomach

• Pancreas

• Small bowel

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.

神经内分泌肿瘤通常见于胃肠道（大肠、小肠或胰腺）或肺内。所以应该考虑这些部位。



Poorly Differentiated CarcinomaPoorly Differentiated CarcinomaPoorly Differentiated CarcinomaPoorly Differentiated Carcinoma

• Diagnoses to consider:

- Adenocarcinomas

- Squamous cell carcinomas

- Neuroendocrine carcinomas

- Hepatocellular carcinoma

- Thyroid carcinoma

- Renal cell

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.

如果发现患者有分化不良的癌症，但无法做进一步的细分，则需要考虑这些各种不同亚型的所有可疑原发部位。

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Poorly Differentiated NeoplasmPoorly Differentiated NeoplasmPoorly Differentiated NeoplasmPoorly Differentiated Neoplasm

• Diagnoses to consider:

- All types of carcinoma

- Lymphoma

- Melanoma

- Sarcoma

- Others

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.

同样，在罕见情况下，如果患者只有分化不良赘瘤的诊断，则必须考虑几乎所有的癌症类型。



ImmunohistochemistryImmunohistochemistryImmunohistochemistryImmunohistochemistry

• 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

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.

免疫组织化学染色可以帮助对肿瘤进行分型，并对可能的原发部位提供更多信息。但是并不建议做一系列的检测。因为这样不仅会增加费用，而且得到的阳性染色列表并不能真的帮助判定原发部位。相反，当临床表现提示考虑不同的原发部位时，一种染色可帮助决定两种癌症中哪一种可能是病因。例如，如果患者有肝脏肿瘤，并接受了活检，则观察染色形态可帮助判定肝脏肿瘤是腺癌还是肝细胞癌。与之类似，黏液腺癌通常见于胃肠道或卵巢，而这两个部位的癌症通常有着极为不同的染色形态。

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Immunohistochemical StainingImmunohistochemical StainingImmunohistochemical StainingImmunohistochemical Staining

• Cytokeratin stains

• PSA, PAP

• TTF 1

• ER/PR

• Gross cystic disease fibrous protein (GCDFP)

• C-kit

• Hep par

• Uroplakin III (UROIII)

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.

免疫组织化学染色方法的种类繁多，我在这里列出了很多种。其中一些较为常见，例如细胞角蛋白染色、PSA、TTF1、ER/PR 等等。



• CK 7: lung, ovary, endometrium and breast

• CK 20: GI tract, urothelium and Merkel cells

Example: CytokeratinExample: CytokeratinExample: CytokeratinExample: Cytokeratin

NCCN GuidelinesTM for occult primary V.1.2010, www.nccn.org

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

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.

有单发肺病灶且曾经有远处结肠癌病史的患者，可以作为使用细胞角蛋白染色的范例。这当然可以是转移性结肠癌或肺原发癌。观察细胞角蛋白 20 和细胞角蛋白 7 的染色形态，通常会看见结肠癌和肺癌具有不同的染色形态。因此，这两种染色方法通常被用来帮助临床医生判定正确的诊断结果，从而显著影响对疾病的治疗与管理。

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Limitation of Pathology ReviewLimitation of Pathology ReviewLimitation of Pathology ReviewLimitation 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

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.

要注意的是，病理学检查可以对诊断患者很有帮助，但是有其局限性。其中一项是采样的局限性。我们之前讨论过，与能够取得更多组织的病理学检查相比，细胞学检查有局限性，产生的费用，进行的更多种染色，以及获得的信息过多有时候反而会产生误导作用。染色方法并非 100% 的敏感或特异，仅仅能够为鉴别两种可能疾病之一提供参考信息和证据。。在查看 H 和 E 染色时，临床情况是指导疾病原发部位总体印象的最重要因素。咨询病理科医生会极有帮助，具体要取决于临床医生和病理科医生的经验。


Staging Staging Staging Staging Approach After Biopsy if Primary Site is Still Approach After Biopsy if Primary Site is Still Approach After Biopsy if Primary Site is Still Approach After Biopsy if Primary Site is Still Not KnownNot KnownNot KnownNot 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

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 given the clinical scenario. The NCCN Guidelines

TM

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.

如果在取得活检结果之后仍无法确认原发部位，则需要重新考虑临床表现。根据这位患者的家族史或其他个人史，是否有罹患特定类型癌症的极高风险？患者表现出的体征和症状如何？是否提示可能的原发疾病部位？是否有任何化验结果支持某种诊断？然后需要做仔细的成像检查，意思是，我们不要求病人做大量的检测，而是根据组织类型和临床状况，要求做适当的检测。对于不常看诊癌症原发病灶不明的医务人员来说，NCCN GuidelinesTM

十分有助于指导这样的评估。还可以考虑咨询病理科医生，看能否提供其他信息跟建议。。

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Tumor MarkersTumor MarkersTumor MarkersTumor 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.

我提到过肿瘤标记物。这些物质见于血液，有时也见于尿液和另一种正常体液。肿瘤标记物对于筛查很有帮助，例如使用 PSA 来筛查前列腺癌，使用甲胎蛋白来筛查肝细胞癌。在对疾病的原发部位做出初始诊断时，肿瘤标记物所起到的作用轻微、有限。肿瘤标记物对于监测已完成治疗，并且感觉疾病处于缓解状态的患者来说极有帮助。如果肿瘤标记物的水平上升，则提示疾病可能复发。还可使用肿瘤标记物来监测正在接受治疗的患者，查看患者是否出现早期疗效，或者查看治疗是否无效。与染色一样，肿瘤标记物并不是完全敏感或特异。有许多肿瘤标记物，例如

CEA，会因为多种恶性疾病而升高。而且肿瘤标记物有时还可受其他因素的影响，例如肝功能或者患者是否吸烟。

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• Hormones

– HCG

– Calcitonin

– Catecholamines

• Enzymes

– PAP

– LDH

– Neuron-specific

enolase

• Antigens

– AFP

– CEA

• Proteins

– PSA

– CA 19-9, 125, 25.27

– CD 30, 25

Tumor MarkersTumor MarkersTumor MarkersTumor Markers

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.

有各种类型的肿瘤标记物。一些是激素、酶、蛋白质或抗原。这里列出了一些，我肯定其中的多数都是大家所熟知的。。



Classification and StagingClassification and StagingClassification and StagingClassification 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)

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.

肿瘤可以根据其行为属性来分型。。因此建立了一套分期系统，有助于进一步指导治疗过程、估测预后，并且对于临床研究具有重要意义，这样我们就可以确保两个不同治疗组内的患者情况类似。

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Staging SystemsStaging SystemsStaging SystemsStaging Systems

• American Joint Committee on Cancer (AJCC) is

the primary staging system for most malignancies

• Pathologic staging

• Clinical staging

– TNM

• Tumor

• Nodes (regional)

• Metastasis

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.

实体肿瘤主要使用美国癌症联合委员会的分期系统，包括病理分期和临床分期。最常使用的是 TNM 分期，即肿瘤外观、区域淋巴结状况和转移状况。



Tumor StageTumor StageTumor StageTumor Stage

Many tumors are staged by size such as:

• Lung

• Breast

• Ovarian

• Prostate

Lung mass on CT scan

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.

根据肿瘤类型，可以按照不同的特点对肿瘤进行分期。对于某些肿瘤来说，我们查看肿瘤的大小，比如说肺癌、乳腺癌、卵巢癌或前列腺癌。超过特定大小的肿瘤，其 T 分期级别更高。

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Tumor StageTumor StageTumor StageTumor Stage

Bowel and bladder cancers as well as melanomas

are staged by depth of penetration

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 T-staging.

这与肠壁内肿瘤一类的肿瘤有所不同。这张内窥镜超声图显示肿瘤穿透了结肠肌层，因此是 T3 期病灶。与膀胱癌和黑色素瘤类似，穿透厚度决定 T 分期。



Nodal StageNodal StageNodal StageNodal Stage

• Nodal stage is based on:

- Number

- Location (regional)

• Distant lymph node involvement

is considered metastasis based

on the presumption that this is

hematologic spread

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.

结节分期与区域淋巴结以及原发肿瘤直接相关区域内的淋巴结位置和数目有关。请注意，如果患者在原发部位的远端出现淋巴结转移，则意味着疾病转移。

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Nodal StageNodal StageNodal StageNodal 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

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.

有时可以通过体检来评估患者的淋巴结，例如黑色素瘤或乳腺癌。再比如头颈癌会引流入颈部区域淋巴结，这样就可以在体检时触及。腹股沟区域淋巴结是肛门癌的引流部位之一。因此这些部位可以而且应该在患者体检时进行评估。。所有患者的初始评估都应该检查所有可触及的淋巴结流域，颈部淋巴结、锁骨上淋巴结、腋窝淋巴结和腹股沟淋巴结，以判断是否有区域或转移性淋巴结累及。



Biopsy or aspiration of nodes may be performed to confirm

involvement when this will affect treatment

Nodes may be assessed by imaging studies such a CT, MRI or

ultrasound based on size and appearance of regional nodes

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.

其他淋巴结可以通过 CT、MRI 或超声波来评估。放射科医生可以根据淋巴结的大小和特点判断是否提示有淋巴结累及。如有必要，可以对可疑淋巴结进行活检或穿刺，以判定淋巴结是否确实被累及，而且只有在检查结果会影响对患者的临床管理时，才应进行这样的活检或穿刺。

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• Regional nodes are most

often staged surgically,

at the time of primary

tumor resection

• Most accurate determination

of lymph node involvement

occurs with:

– Evaluation at the time

of surgery

– Adequate lymph

node dissection

– Thorough pathologic review

Node StagingNode StagingNode StagingNode Staging

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.

累及淋巴结最常在手术切除原发部位肿瘤时被识别并诊断，而且这可以提供最准确、最有用的信息，尽管有时需要在术前判断是否有累及淋巴结。



MetastasisMetastasisMetastasisMetastasis

• 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

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.

当然可以根据临床检查或表现症状，怀疑出现转移。如果患者有器官肿大或者有可触及的肿块，例如腹内肿块或软组织肿瘤，这毫无疑问提示可能有转移性疾病。应该依据特定肿瘤类型的通常转移扩散部位来决定临床评估以及患者应该接受的诊断性检测。有公认的指南为特定肿瘤类型的恰当评估提供指导。很少需要进行外科评估来确认是否存在转移，但偶尔需要进行外科评估，或者会在患者接受手术时同时进行外科评估。

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Common Imaging Studies for Cancer StagingCommon Imaging Studies for Cancer StagingCommon Imaging Studies for Cancer StagingCommon Imaging Studies for Cancer Staging

• CT

• MRI

• Ultrasound

• Bone scan

• PET scan

There are number of common imaging studies that are used in the evaluation of cancer patients, CT, MRI, ultrasound, PET scan, and bone scan.

有一些用于评估癌症患者的常见影像学检查方法，例如 CT、MRI、超声、PET 扫描和骨扫描。



Computed Tomography ScanComputed Tomography ScanComputed Tomography ScanComputed 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

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.

CT 扫描会取得横截面图像，截面宽度通常介于 3 至

5 毫米之间，有时是 10 毫米。CT 扫描需要静脉注射造影剂，而口服造影剂一般用来评估腹部或骨盆。如果患者肾功能受损，则有时会有禁忌症，以静脉注射造影剂尤甚。

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CT ScanCT ScanCT ScanCT Scan

• Commonly used in imaging of:

– Lungs

– Liver

– Pancreas

– Brain

– Lymph nodes

Hypodense lesion in the

liver consistent with

hepatic metastasis

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.

CT 扫描常用于评估肺、肝、胰腺、大脑和淋巴结。这里的例子是 CAT 扫描显示的肝内病灶。



Magnetic Resonance ImagingMagnetic Resonance ImagingMagnetic Resonance ImagingMagnetic Resonance Imaging

• Use of radio frequency

signals to produce

an image

• Requires enclosure in

MRI machine

• Open MRI images inferior

to closed machine

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.

MRI 使用射频信号来产生图像。接受 MRI 检查时患者需要处于封闭式 MRI 机器内。尽管有开放式 MRI 机器，但其效果要劣于封闭式机器，对于管理和评估癌症患者几乎没有帮助。有些患者需要镇静才能进入封闭式 MRI 机器。

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MRIMRIMRIMRI

• Useful for CNS or soft

tissue lesions

• Also used for body

imaging

• May help to distinguish

types of hepatic lesions

Choroid Plexis Papillomas

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.

MRI 对于检查中枢神经系统肿瘤和软组织肿块尤为有帮助。MRI 还可用于之前提及的所有其他 CT 扫描部位，例如大脑、肺和肝脏。MRI 对于区分特定类型的肿瘤，区分肿瘤内不同特点（例如肝肿瘤内的特点）尤其有帮助。所以有时候进行 MRI 可以在 CAT 扫描的基础上获得更多的信息。



UltrasoundUltrasoundUltrasoundUltrasound

• Avoids risk of radiation or contrast

• Can be performed:

– Percutaneously

– Endoscopically

– Intraoperatively

Ultrasound avoids the risk of radiation and contrast. It can be performed percutaneously, endoscopically, or intraoperatively.

超声可以避免放射和造影剂所带来的风险。可以经由皮肤，通过内窥镜，或在手术期间进行超声检查。

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UltrasoundUltrasoundUltrasoundUltrasound

• Help to distinguish cystic vs. solid tumors

such as hepatic lesions

• Can provide complementary information

to radiographs

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.

超声对于区分囊性肿瘤和实体肿瘤很有帮助，比如说通常发生囊性病灶的乳腺、卵巢和肝脏。超声可以在

CT 或 MRI 的基础上提供补充信息。



Bone ScanBone ScanBone ScanBone Scan

• Nuclear medicine study

• Detects patient injected tracer

• Identifies areas of high bone turnover

• Surveys full skeleton

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.

骨扫描是一种核医学检查。接受骨扫描时患者需要注射示踪剂。示踪剂可以显示骨转换水平较高因而可能有恶性病变的区域，不过其他病症也可能造成这样的异常显示。骨扫描的优势之一是可以检查全身骨骼。所以如果患者的恶性疾病通常有骨转移，这种检查方法就很有用。

23



Bone ScanBone ScanBone ScanBone Scan

• 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

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.

骨扫描可以探测出骨病的原发部位以及骨的转移性病变。骨扫描对于溶骨病灶尤为有帮助，而对于成骨病灶的帮助不大。



PET ScanPET ScanPET ScanPET 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

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.

PET 扫描是另一种核医学检查方法，它是在向患者注射示踪剂之后探测发射的正电子，从而获得生理图像。用放射示踪剂同位素标记 FDG，发射出会衰变的正电子，从而识别出体内新陈代谢活动水平较高因而可能有恶性病变的部位。但是，诸如炎症或传染病等其他病症也可以使 PET 扫描图像的亮度增高。

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PET Scan Use in StagingPET Scan Use in StagingPET Scan Use in StagingPET Scan Use in Staging

• Can identify other possible

sites of disease, lymph nodes

and distance metastatic

disease

• 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.

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.

对于一系列不同的癌症来说，PET 扫描更常用于分期。PET 扫描可以识别疾病的可能部位，包括淋巴结累及和转移性疾病。PET 扫描常规结合 CAT 扫描使用，可以针对累及部位提供更为详细的解剖信息。



ConclusionsConclusionsConclusionsConclusions

• 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

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.

总而言之，大多数癌症的诊断需要审查通过活检或穿刺获得的病理检查信息。判定肿瘤的原发部位需要考虑疾病的临床表现、病理学审查结果，还需考虑转移扩散的模式。癌症分期是评估恶性疾病患者非常重要的一步，以预估其预后。癌症分期可以帮助指导治疗建议，还可以对参加临床试验的患者进行分层。我们今天的讲座就到此结束。我们希望这次讲座对大家有帮助。欢迎提出宝贵意见。

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