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APPROACH  TO  THE  CORPUS  BIOPSY  Premalignant  and  Malignant  Lesions  

EIN  and  Hyperplasia  

Joseph  Carlson,  MD,  PhD    

joseph.carlson@karolinska.se  

Karolinska  Universitetslaboratoriet    Klinisk  patologi/cytologi    

Good  References  1. McCluggage  WG.  My  approach  to  the  interpretaOon  of  

endometrial  biopsies  and  curePngs.  J  Clin  Pathol.  2006  Aug;59(8):801-­‐12.  Review.  PubMed  PMID:  16873562;  PubMed  Central  PMCID:  PMC1860448.  

2.  Online  web  seminars  at  www.endometrium.org  

3. Mazur  and  Kurman.  Diagnosis  of  Endometrial  Biopsies  and  CurePngs:  A  PracOcal  Approach.  Springer.  2004.  

4. Malpica,  Deavers,  Euscher.  Biopsy  InterpretaOon  of  the  Cervix  and  Corpus.  Lippincoc  Williams  &  Wilkins.  2009.  

Clinical  History  

•  Age  •  IndicaOon  •  Premenopausal:  LMP,  cycle  length  •  Hormone  status  (HRT,  p-­‐piller)  

Adequacy  

•  Inadequate:  Only  if  no  endometrial  Ossue  is  present  at  all.  

•  Atrophy:  Postmenopausal  women,  no  finding  on  ultrasound,  minimal  Ossue  is  normal.  

•  Too  licle  to  assess:  Minimal  Ossue  where  one  would  expect  more  (premenopausal,  thickened  endometrium  on  ultrasound,  polyp  or  other  hysteroscopic  finding)  

 

McCluggage  WG.  My  approach  to  the  interpretaOon  of  endometrial  biopsies  and  curePngs.  J  Clin  Pathol.  2006  Aug;59(8):801-­‐12.  Review.  PubMed  PMID:  16873562;  PubMed  Central  PMCID:  PMC1860448.  

Artefacts  

Can  mimic  papillary  growth,  complex  architecture,  atypia.  

Look  at  benign  biopsies  and  learn  from  them.    As  a  resident,  you  study  cancer  and  try  to  classify  it.  

As  an  acending,  you  study  all  the  surrounding  normal  Ossues,  and  learn  about  artefacts  and  normal  variaOon.  

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Pseudopapillary  artefact    Artefact  

Artefact   Telescoping  artefact  

Artefact  –  Mimics  “Oght  glands”,  loss  of  stroma  

Meningioma  mixed  with  EMBx.  Neuro  specimens  and  biopsies  cut  in  on  the  same  bench.  This  was  contaminaOon.  

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Non-­‐endometrial  Ossues  

Cervix:  Evaluated  and  described  Fat:  Can  indicate  uterine  perforaOon.  Should  be  described  and  signed  out  acutely  (possible  contact  with  clinician).  

Lower  uterine  segment:  Can  resemble  polyp  Other:  myometrium  

Fat  on  EMBx.  Can  indicate  perforaOon  and  clinician  should  be  called.  

Metaplasia  

Squamous  –  usual  and  morular  Mucinous  Eosinophilic  Tubal  (ciliated  cell)  Papillary  syncyOal    

Squamous  metaplasia  

Should  not  be  counted  as  “solid  growth”  Can  mimic  “clear  cells”  due  to  glycogen  Can  be  due  to  reacOve  cause  (endometriOs),  premalignant  or  malignant.  

Morules  can  have  central  necrosis  Morules  on  biopsy  need  follow  up  to  exclude  a  malignant  process.  

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Mucinous  metaplasia  

Typically  resembles  endocervix  Minimal  atypia  Classified  by  architecture:    Simple  epithelium  –  low  risk  of  cancer    Cribriform,  papillary  architecture  –  higher  risk  of  cancer.  

Mimics:  Cervical  microglandular  hyperplasia  

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Features  typically  found  in  endometrial  mucinous  metaplasia.  

Cervical  Microglandular  Hyperplasia  

Endometrial  Mucinous  Metaplsia  

Prominent  subnuclear  vacuoles  

PRESENT   ABSENT  

Luminal  squamous  metaplasia  

ABSENT   PRESENT  

Stromal  foam  cells   ABSENT   PRESENT  MitoOc  index   LOW   HIGH  (>3  per  10  HPF)  VimenOn  staining   ABSENT   PRESENT  Reserve-­‐like  cells  in  surrounding  epithelium  

PRESENT   ABSENT  

Qiu  W,  Mical  K:  Comparison  of  morphologic  and  immunohistochemical  features  of  cervical  microglandular  hyperplasia  with  low-­‐grade  mucinous  adenocarcinoma  of  the  endometrium.  Int  J  Gynecol  Pathol    2003;  22:261-­‐265.  

Eosinophilic  metaplasia  

Cuboidal  cells  with  pink  cytoplasm    Architecture  determines  risk.  

Tubal  metaplasia  

Associated  with  elevated  estrogen.    Common  in  the  lower  uterine  segment.    Low  cancer  risk  if  architecture  is  simple.  

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Papillary  syncyOal  metaplasia  

Menopausal  women  on  hormone  replacement  therapy.  

Onen  associated  with  REPAIR.  Onen  overlying  STROMAL  BREAKDOWN.  IndisOnct  cell  borders  (syncyOum),  eosinophilic  cytoplasm,  loss  of  nuclear  polarity.  

MUST  EXCLUDE  CARCINOMA  

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Hyperplasia  

Exclude  benign  mimics  

1994  WHO  

Terminology  to  avoid  in  the  endometrium:    Dysplasia      CysOc  hyperplasia    Adenomatous  hyperplasia    Adenocarcinoma  in  situ  

Hyperplasia  

CombinaOon  of  architecture  (complex,  simple)  and  atypia  (present,  absent)  

No  atypia   Atypia  Simple   Hormones  

(1-­‐2%  cancer  risk)  RARE  

Complex   RARE   Hysterectomy    (25-­‐40%  cancer  risk)  

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“Simple  with  atypia”  AND  “Complex  without  atypia”  are  very  rare!   Hyperplasia  -­‐  Architecture  

Simple:      Gland  to  stroma  raOo  is  maintained.  

Complex:      Increased  gland  to  stromal  raOo.  

Simple  Hyperplasia  without  Atypia  

EssenOally  an  estrogen  effect.  No  real  difference  from  “anovulaOon”  as  described  in  lecture  1.  

Regular  irregular  gland  pacern,  dilated  glands.  Typically  diffuse  –  all  the  glands  are  affected  by  the  estrogen.  

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Complex  Hyperplasia  

 Increased  gland  to  stromal  raOo.      You  do  not  need  more  than  that!  

SIMPLE  ARCHITECTURE    (VOLUME  PERCENT  STROMA  HIGH)  

COMPLEX  ARCHITECTURE    (VOLUME  PERCENT  STROMA  LOW)  

www.endometrium.org  

Atypia  

No  atypia:      Gland  to  stroma  raOo  is  maintained.  

Atypia:      “One  of  the  most  subjecOve  and  problemaOc  areas  of  gyn  pathology”.  

 

Hyperplasia  -­‐  Atypia  

Comparison  of  suspected  glands  with  background  normal  

 Nuclear  features:  StraOficaOon,  loss  of  polarity,  rounding  and  nucleoli  

 Cytoplasmic:  Abundant,  eosinophilic,  cytoplasm    

Complex  Atypical  Hyperplasia  

Typically  a  focal  process  (i.e.  there  are  preserved  normal  glands  in  the  background).  

 This  is  a  reflecOon  of  the  fact  that  it’s  a  neoplasm.  

www.endometrium.org  –  EIN  Diagnosis  Library  Complex  Atypical  Hyperplasia  

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www.endometrium.org  –  EIN  Diagnosis  Library  Complex  Atypical  Hyperplasia  

www.endometrium.org  –  EIN  Diagnosis  Library  Complex  Atypical  Hyperplasia  

www.endometrium.org  –  EIN  Diagnosis  Library  Complex  Atypical  Hyperplasia  

www.endometrium.org  –  EIN  Diagnosis  Library  Complex  Atypical  Hyperplasia  

DisOncOon  Between  Hyperplasia  and  Cancer  

Spectrum  of  changes  May  be  impossible  on  small  biopsies    “at  least  atypical  hyperplasia,  cannot  exclude  grade-­‐1  endometrioid  carcinoma”  

DisOncOon  Between  Hyperplasia  and  Cancer  

1.  Maze-­‐like  meandering  glands  /  Rambling  glands  /  Bridging  between  adjacent  glands  

2.  Solid  non-­‐squamous  areas  3.  Cribriform  areas  4.  Gaping  glands  /  mosaic  pacern  

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Thank  you!