Evaluation of suspected malignancies: Difference between revisions
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{{Top | <noinclude>{{Top | ||
|author1=[[User:Mikael Häggström|Mikael Häggström]] | |author1=[[User:Mikael Häggström|Mikael Häggström]] | ||
|author2= | |author2= | ||
}} | }}</noinclude> | ||
For [[evaluation]] of '''suspected malignancies''' such as '''tumors''', the most important aspect is whether it is benign or malignant. If malignant, then staging is necessary.<ref name=cancer>{{cite web |url= http://www.cancer.gov/cancertopics/factsheet/detection/staging |title=Cancer staging |date= |publisher=National Cancer Institute |accessdate=4 January 2013}}</ref> There are generally specific criteria for various forms of tumors, which should be used whenever applicable, but following are some generalizations. | For [[evaluation]] of '''suspected malignancies''' such as '''[[tumors]]''', the most important aspect is whether it is benign or malignant. If malignant, then staging is necessary.<ref name=cancer>{{cite web |url= http://www.cancer.gov/cancertopics/factsheet/detection/staging |title=Cancer staging |date= |publisher=National Cancer Institute |accessdate=4 January 2013}}</ref> There are generally specific criteria for various forms of tumors, which should be used whenever applicable, but following are some generalizations. | ||
A general approach is to start looking at | A general approach is to start looking at a slide which seems to contain non-necrotic tumor, and if possible it should also show surrounding non-tumor tissue, so that the interface can be appreciated (and tumors are generally less necrotic at the periphery). | ||
==Benign or malignant== | ==Benign or malignant== | ||
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File:Nuclear-to-cytoplasm ratios.png|An increased nucleus-cytoplasm ratio is generally an indication of malignancy. | File:Nuclear-to-cytoplasm ratios.png|An increased nucleus-cytoplasm ratio is generally an indication of malignancy. | ||
</gallery> | </gallery> | ||
{{Primary tumor versus metastasis}} | |||
== | <br>{{further|Metastasis}} | ||
For specific diagnoses by organ system, see anatomic diagram on Patholines '''[[Main page]]'''. This resource will give the main steps towards reaching a diagnosis, but before making a tumor diagnosis, | ==Histopathologic type== | ||
For specific diagnoses by organ system, see anatomic diagram on Patholines '''[[Main page]]'''. This resource will give the main steps towards reaching a diagnosis, but before making a tumor diagnosis, generally be sure that it fulfills the criteria of the condition according to [https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours The WHO Classification of tumors], and generally consult an experienced pathologist as well until you feel confident. | |||
Visually, tumors and other suspected malignancies can usually be classified into one of the following groups: | Visually, tumors and other suspected malignancies can usually be classified into one of the following groups: | ||
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Further pinpointing of a specific tumor type is often attained by thinking of one or more possible diagnoses, and looking up their '''differential diagnoses''', followed by comparing their microscopic descriptions and multiple micrographs with the case at hand. When two or more diagnoses seem to fit with the case at hand, consider performing '''immunohistochemistry'''. Find relevant target proteins that are expected to stain substantially differently between the possible diagnoses. If it's not evident from initial sources, you may use Immunoquery.com which will generally suggest the most relevant target proteins to distinguish the suspected conditions at hand. | Further pinpointing of a specific tumor type is often attained by thinking of one or more possible diagnoses, and looking up their '''differential diagnoses''', followed by comparing their microscopic descriptions and multiple micrographs with the case at hand. When two or more diagnoses seem to fit with the case at hand, consider performing '''immunohistochemistry'''. Find relevant target proteins that are expected to stain substantially differently between the possible diagnoses. If it's not evident from initial sources, you may use Immunoquery.com which will generally suggest the most relevant target proteins to distinguish the suspected conditions at hand. | ||
===Gland-like tumors=== | |||
[[File: | [[File:Histopathology of adenocarcinoma.png|thumb|250px|Typical features of adenocarcinomas. In reality, the appearance varies significantly from case to case. Vacuoles are more prominent in mucinous tumors, but can be seen in serous tumors as well.]] | ||
Gland-like tumors are mainly evaluated for cellular atypia, architectural dysplasia and invasion, and thereby classified into the following main categories: | Gland-like tumors are mainly evaluated for cellular atypia, architectural dysplasia and invasion, and thereby classified into the following main categories: | ||
*'''Hyperplastic''' lesions, lacking significant atypia | *'''Hyperplastic''' lesions, lacking significant atypia | ||
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:*[[Esophageal adenocarcinoma]] | :*[[Esophageal adenocarcinoma]] | ||
:*[[Endometrial adenocarcinoma]] | :*[[Endometrial adenocarcinoma]] | ||
:*[[Pancreatic ductal adenocarcinoma]] | |||
[[File:Well-, moderately and poorly differentiated colorectal adenocarcinoma.png|thumb|370px|Degree of differentiation, with example from a [[colorectal adenocarcinoma]].]] | |||
Generally, adenocarcinomas are categorized by degree of '''differentiation''' as follows: | |||
*Well differentiated: > 95% of tumor has glandular formations | |||
*Moderately differentiated: 50 - 95% glandular | |||
*Poorly differentiated: < 50% glandular | |||
If '''[[Metastasis|metastatic]] adenocarcinoma''' seems to be the case (always consider this in at least [[lung adenocarcinoma]]), look at the history and radiology reports for a most likely primary. Generally, perform [[immunohistochemistry]] with one or two stains that are most typical for the suspected primary, and optionally add CK7 and CK20 as a broad screening. {{further|Metastasis}} | |||
===Squamoid tumors=== | |||
These are more or less looking like a '''[[squamous-cell carcinoma]]''': | These are more or less looking like a '''[[squamous-cell carcinoma]]''': | ||
<gallery mode=packed heights=220> | <gallery mode=packed heights=220> | ||
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*Cervix uteri: '''[[Cervical dysplasia]]''' | *Cervix uteri: '''[[Cervical dysplasia]]''' | ||
===Spindle-cell tumors=== | |||
For '''Spindle-cell tumors''', the shape of the nuclei is a clue to the diagnosis, with the following tendency: | For '''Spindle-cell tumors''', the shape of the nuclei is a clue to the diagnosis, with the following tendency: | ||
*Pointed on both ends: True fibroblastic tumors | *Pointed on both ends: True fibroblastic tumors | ||
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*'''[[Soft tissue tumor]]'''</noinclude> | *'''[[Soft tissue tumor]]'''</noinclude> | ||
=== | ===Further histopathologic subtyping and grading=== | ||
Beyond determining overall malignancy diagnosis (such as adenocarcinoma), probable origin and staging, classification of tumors into a specific histopathologic type or grade is generally of relatively less value. In cases of clearly non-malignant tumors where it is difficult to determine the specific histopathologic type or grade, it is generally acceptable to conclude the evaluation and report it as such, unless the clinician specifically requests otherwise. For potentially malignant or high-risk tumors, typing and grading often still affects the management, but generally much less so than staging. | |||
=== | {{Undifferentiated malignancy}} | ||
===Non-neoplastic=== | |||
If a '''neoplasm has been ruled out''' for what clinically appeared like a tumor, seek a diagnosis that can be consistent with the clinical findings that caused the suspicion. If no explanation is found on the slides, generally take additional levels on the paraffin block, or more sections from any leftover tissue. | If a '''neoplasm has been ruled out''' for what clinically appeared like a tumor, seek a diagnosis that can be consistent with the clinical findings that caused the suspicion. If no explanation is found on the slides, generally take additional levels on the paraffin block, or more sections from any leftover tissue. | ||
For example, for a breast biopsy of what appeared to look like a mass, and there is no neoplasia, look mainly for dense fibrosis or other fibrous changes, so that you can report it and thereby explain the finding, rather than merely writing "benign breast tissue". | For example, for a breast biopsy of what appeared to look like a mass, and there is no neoplasia, look mainly for dense fibrosis or other fibrous changes, so that you can report it and thereby explain the finding, rather than merely writing "benign breast tissue". | ||
===Heterogeneity=== | |||
After having characterized a suspected malignancy, still screen through it for any significant areas that are different and may need own mentioning, or even change the overall type or grade. | |||
==Additional levels or slices== | ==Additional levels or slices== | ||
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** N2: tumor spread to an extent between N1 and N3 (N2 is not used at all sites) | ** N2: tumor spread to an extent between N1 and N3 (N2 is not used at all sites) | ||
** N3: tumor spread to more distant or numerous regional lymph nodes (N3 is not used at all sites) | ** N3: tumor spread to more distant or numerous regional lymph nodes (N3 is not used at all sites) | ||
'''M''': presence of distant metastasis | '''M''': presence of distant metastasis {{Further|Metastasis}} | ||
** M0: no distant metastasis | ** M0: no distant metastasis | ||
** M1: metastasis to distant organs (beyond regional lymph nodes) | ** M1: metastasis to distant organs (beyond regional lymph nodes) | ||
|} | |} | ||
[[File:Histopathology of a lymph node with metastatic invasive ductal carcinoma from the breast.jpg|thumb|220px|For positive lymph nodes, generally also note any '''extranodal extension''', and the size thereof.]] | |||
Put your main '''focus''' on features that will determine the final stage. For example, if you see a lymph node involved by cancer, the presence or absence of lymphatic invasion is no longer critical, but rather the presence or absence of additional involved nodes or distant metastasis. If a stage-defining finding is uncertain, generally fall back to the lower stage. | |||
For the '''size''', the greatest dimension of the tumor is most important. Second and third dimensions (preferably at right angles compared to each other) are optional. Use the largest measure for each dimension. For example if one slide shows a tumor measuring 2.0 x 1.0 cm, and another slide shows the same tumor measuring 1.5 x 1.5 cm, then the tumor can be reported as measuring 2.0 x 1.5 cm. The third dimension can be estimated from gross measurement, or, if the tumor is entirely submitted, adding together the presumed thickness of each slice where tumor is found microscopically. For excisions with less than a centimeter of tumor, and where there has been a previous biopsy, consider looking at the size of tumor on the previous biopsy, which may be the largest measurement, and therefore the measurement of choice for staging. | |||
'''Nx: lymph nodes cannot be assessed''' also applies when you only find lymph nodes that are not within the physiologic drainage path of the cancer, and they are benign. | |||
==Radicality== | ==Radicality== | ||
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</gallery> | </gallery> | ||
== | ==Molecular workup== | ||
Ensure that any cancer undergoes reflex testing where applicable by local guidelines. When they are not applicable, a rule of thumb is to order individual genetic testing if there is a need to test up to 2 genetic targets, and to order genomic sequencing if more targets need genetic testing (not counting [[immunohistochemitry]] or other more easily performed tests). | |||
When needing to '''send out''' tissue to an outside laboratory, follow their requirements and guidelines for each test. Generally, choose the tissue block with the greatest amount/area of the highest grade malignancy. For molecular proliferation tests (other than [[immunohistochemistry]]) such as Ki67, avoid samples with previous biopsy site or inflammation (as these will cause a false high proliferation rates). On the other hand, for next-generation sequencing, hemorrhage, necrosis and adipose tissue does not need to be minimized, as these contain only little genetic material. | |||
==Reporting== | |||
[[File:Histopathology of pancreatic adenocarcinoma with treatment effect.jpg|thumb|Also note "treatment effect", seen as fibroelastotic tissue, here with scattered remaining tumor cells.]] | [[File:Histopathology of pancreatic adenocarcinoma with treatment effect.jpg|thumb|Also note "treatment effect", seen as fibroelastotic tissue, here with scattered remaining tumor cells.]] | ||
{{CAP}} If there is no CAP synoptic available for the cancer type at hand, attempt to find one in the latest AJCC Cancer Staging Manual (see the [[Secrets]] article), but make sure to use pathologic staging (with a p preceding the T, N or M) rather than clinical staging. | |||
If a surgery produces a specimen with cancer, as well as re-excisions from certain directions, you should preferably give the closest distance to margins in each specimen, as well as the closest distance overall in a synoptic, for example: | If a surgery produces a specimen with cancer, as well as re-excisions from certain directions, you should preferably give the closest distance to margins in each specimen, as well as the closest distance overall in a synoptic, for example: | ||
{|class=wikitable | {|class=wikitable | ||
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*Closest margin(s) to invasive carcinoma: Lateral | *Closest margin(s) to invasive carcinoma: Lateral | ||
|} | |} | ||
If possible, generally include features of any '''previous biopsies''' or smaller excisions in synoptic reports and staging. For example, if staging is based on tumor size, and the tumor size in a previous excisional biopsy corresponds to a higher stage than the size of residual tumor in a subsequent wider excision, then the report of the latter should give the higher stage, with a comment thereof, such as: | |||
:pT__ | |||
:- Based on previous excisional biopsy (specimen ID: ______) | |||
{{Reporting}} | {{Reporting}} | ||
<noinclude> | <noinclude> | ||