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18 Rabban Uterine Cancer APractical Approach To Histologic Subtyping
18 Rabban Uterine Cancer APractical Approach To Histologic Subtyping
18 Rabban Uterine Cancer APractical Approach To Histologic Subtyping
Uterine Cancer:
5/25/2013
Trial of
Hormone
Therapy
Or
Hysterectomy
g1 Endometrioid, no Myoinvasion/LVI
g1 Endometroid, +Myoinvasion
Plus omentectomy:
Serous carcinoma
Carcinosarcoma
None
Chemotherapy
considered
Radiation
considered
Ifosfamide
considered
Etoposide
considered
neuroendocrine carcinoma
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Sub-typing
Grading
Tumor infiltrating lymphocytes
Peritumoral lymphocytes
Undifferentiated histology
Lower uterine segment origin
Concurrent ovarian cancer
Staging
Lynch syndrome tumor morphology and testing
Endometrioid adenocarcinoma
Serous carcinoma
Clear cell carcinoma
Transitional cell carcinoma
Mucinous carcinoma
Small cell carcinoma
Squamous cell carcinoma
Undifferentiated carcinoma
Carcinosarcoma
Mixed type (each type must be > 10% overall tumor)
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Outline of Talk
Practical issues:
Problematic variations: A pattern-based approach
Immunostain pearls and pitfalls
Newer non-WHO definition of undifferentiated uterine carcinoma
Endometrioid adenocarcinoma
Serous carcinoma
Clear cell carcinoma
Transitional cell carcinoma
Mucinous carcinoma
Small cell carcinoma
Squamous cell carcinoma
Undifferentiated carcinoma
Carcinosarcoma
Mixed type (each type must be > 10% overall tumor)
Evaluate in order :
Clinical context:
Low magnification:
Architecture
High magnification:
Cytology
Adjacent tissue:
Precursor lesion
If needed:
Immunohistochemistry
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Premenopause
Precursor
lesion
IHC
Endometrioid,g1,2
yes
Atypical hyperplasia
Endometrioid,g3
uncommon
Atypical hyperplasia
Serous
uncommon
Serous EIC
p53, p16
Clear cell
uncommon
HNF
Undifferentiated
uncommon
EMA/Keratin loss
Pure glandular
Pure glandular
Papillary
Papillary
Spindled
Spindled
Clear cell-rich
Clear cell-rich
Mucin-rich
Mucin-rich
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Pure glandular
Papillary
Solid, with high grade nuclei
Spindled
Clear cell-rich
Mucinous
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Endometrioid carcinoma
Nucleoli
Grade 1
Endometrioid
Architectural
Grade
Nuclear
Grade
Serous carcinoma
irregular, large, cherry-red
Pseudoglandular
Serous
Low
Low
Low
High
Discordant architecture
versus nuclear grade
Pleomorphic nuclei
Cherry-red macronucleoli
Smudge cells
Atypical mitoses
Normal
N/C ratio
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Adenomyosis
Atrophy
Nuclear
Grade
Serous
Carcinoma
Myoinvasion by
Pseudoglandular
Serous cancer
Low
Low
Low
High
Discordant architecture
versus nuclear grade
Pleomorphic nuclei
Cherry-red macronucleoli
Smudge cells
Atypical mitoses
Gaping
glands
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Grade 1
Endometrioid
Architectural
Grade
Pseudoglandular
Serous
Low
Low
Nuclear
Grade
Low
High
p16, p53
Wild type
Aberrant
ER
Diffuse, strong
Variable
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90 %
Completely negative
88 %
Completely negative
20 %
Stain Interpretation
Aberrant p53
Meaning
Favor serous carcinoma
Aberrant p53
Patchy p16
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p53
Diffuse, strong
p16
Diffuse, strong
p53
p16
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p53
p16
PTEN Mutation
Common in endometrioid carcinoma
Uncommon in non-endometrioid carcinoma
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PTEN Mutation
Endometrioid cancer
PTEN complete negative
Normal endometrium
Hyperplasia
Atypical hyperplasia
Endometrioid cancer
Rare
~30%
~75%
~60-75%
Non-endometrioid cancer
~25-35%
Serous carcinoma
PTEN present
Glandular
Papillary
Solid, with high grade nuclei
Spindled
Clear cell-rich
Yes
No
Mucin-rich
Necrosis, desmoplasia in a biopsy with low grade architecture
Diagnosis
is
Confirmed
Rule out
Serous
Carcinoma
p53
p16
ER
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Serous Carcinoma
Papillary variant
Endometrioid
Carcinoma
Architectural
Grade
Nuclear
Grade
Papillary
Serous
Carcinoma
Low
Low
Low
High
Discordant architecture
versus nuclear grade
Papillary variant
Endometrioid
Carcinoma
Architectural
Grade
Nuclear
Grade
Pleomorphic nuclei
Cherry-red macronucleoli
Smudge cells
Atypical mitoses
Papillary
Serous
Carcinoma
Low
Low
Low
High
p53, p16
wild type
aberrant
ER
diffuse, strong
variable
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Serous carcinoma
Grade 3 endometrioid adenocarcinoma
Undifferentiated uterine carcinoma
Neuroendocrine carcinoma
Undersampled carcinosarcoma
Consider non-epithelial malignancies:
Leiomyosarcoma
Rhabdomyosarcoma
Lymphoma
Melanoma
Solid
Serous
Carcinoma
Columnar/polarized cells
Focal
No
Tubular, glandular
Focal
No
Squamous differentiation
Focal
No
No
Focal
No
Yes
No
Yes
Precursor lesion
Hyperplasia
EIC
Aberrant p53/p16
Sometimes
Yes
PTEN
Lost
Present
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Serous EIC
Atrophy
Atrophy
p53
p53
Consensus Diagnosis
Endometrioid
Serous
p53 Staining
p53 Normal
p53 Positive
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Serous carcinoma
Definition:
Undersampled carcinosarcoma
Leiomyosarcoma
Rhabdomyosarcoma
Lymphoma
Melanoma
Significance:
Highly aggressive / fatal
UUC worse than grade 3 endometrioid
DDUC worse than grade 2 endometrioid
Cytology:
Cytology:
Immunostains:
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Keratin:
Moderate atypia
Rhabdoid cells
Undifferentiated
Low grade
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Low grade
40% to 60% die
Median survival is 6 months
Most deaths are within 5 years
For dedifferentiated uterine carcinoma, prognosis is the same
even if only 20% is undifferentiated carcinoma
Treatment:
Same as for high grade cancer
Often MSI-high so testing for Lynch syndrome is advised
Practical issues:
UUC
A diagnosis of exclusion.
Grade 3
Endometrioid
Tubules, glands
No
Usually focally
Squamous differentiation
No
Focally
Geographic necrosis
Common
Rare
Non-cohesive cells
Yes
No
Rhabdoid cells
Yes
No
Keratin/EMA
<10% cells
Diffuse
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UUC
Serous
Carcinoma
Papillary growth
No
Usually focally
No
Focally
Nuclei
Monotonous
Pleomorphic
Geographic necrosis
Common
Rare
Non-cohesive cells
Yes
No
Rhabdoid cells
Yes
No
Keratin/EMA
<10% cells
Diffuse
Glandular
Papillary
Solid, with high grade nuclei
Spindled
Clear cell-rich
Hobnail , papillary, clear cell
Mucinous
Necrosis, desmoplasia in a biopsy with low grade architecture
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Carcinosarcoma
Spindled types
Endometrioid
Carcinoma
Spindled/sarcomatoid type
Corded and hyalinized type
Progestin-treated type
Arising in atypical polypoid adenomyoma
Carcinosarcoma
Atypia
Lower grade
High grade
Yes
No
Heterologous elements
No
Common
No
Yes
Carcinosarcoma
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Desmin
Myogenin
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30
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Glandular
Papillary
Solid, with high grade nuclei
Spindled
Clear cell-rich
Mucin-rich
Necrosis, desmoplasia in a biopsy with low grade architecture
Endometrioid
Carcinoma
With Clear Cells
Clear Cell
Carcinoma
Cell shape
Columnar
Polygonal
Cell polarity
Preserved
Lost
Tubulocystic plus
papillary growth
Not common
Yes
Hyaline globules
No
Yes
Hyalinized stroma
No
Yes
Hobnail growth
No
Yes
No
Yes
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Hyaline droplets
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Positivity
OVARY
UTERUS
94 - 98 %
73 - 100 %
Endometrioid
0 - 40 %*
0 - 35 %*
Serous
0 - 30 %*
0 - 60 %*
Secretory phase
Gestational phase
Arias Stella reaction
<10 %
p53
variable
p16
<50%
HNF-1
>75%
HNF-1 Expression
Clear cell
ER
HNF-1
positive
*weak/patchy staining
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p53
Aberrant
p16
Aberrant
ER
Positive
HNF
Negative
ARID1A Mutation
Common in Clear Cell Cancer
Endometrioid Cancer
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ARID1A Mutation
29 %
Endometrioid, grade 3
39 %
26 %
Serous carcinoma
18%
Glandular
Papillary
Endocervical adenocarcinoma
Spindled
Clear cell-rich
Mucin-rich
Necrosis, desmoplasia in a biopsy with low grade architecture
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Glandular
Papillary
Solid, with high grade nuclei
Spindled
Clear cell-rich
Mucin-rich
Necrosis, desmoplasia in a biopsy with low grade architecture
Degenerative changes
Myoinvasive grade 1 endometrioid tumor
Myoinvasive pseudo-glandular serous carcinoma
Under-sampled higher grade tumor
Grade 2 or 3 endometrioid carcinoma
Dedifferentiated uterine carcinoma
Carcinosarcoma
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5/25/2013
Grade 1
Grade 3
Report as:
Adenocarcinoma with extensive necrosis; see comment.
Adenocarcinoma with desmoplastic stroma; see comment.
Discuss possibilities of higher grade or higher stage tumor.
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5/25/2013
Outline of Talk
Practical issues:
Problematic variations: A pattern-based approach
Immunostain pearls and pitfalls
Newer non-WHO definition of undifferentiated uterine carcinoma
41