Surgical Pathology Criteria–

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Supplemental Studies

Immunohistology and Histochemical Stains

• PASd shows granular cytoplasmic and/or intracytoplasmic lumenal staining
• Lacks abundant glycogen
• Alcian Blue may highlight intracytoplasmic lumenal borders

Keratin	positive
EMA	positive, highlights intracytoplasmic lumens
GCDFP15	positive
CD68, HAM56, Lysozyme	negative
S100	negative, one case reported weak positive
E cadherin	3/11 positive

 

• Demonstration of myoepithelial cells can confirm the in situ nature of a process while their absence supports invasion
  • We prefer to use both p63 and calponin on problematic cases
  • A variety of markers have been used for myoepithelial cells:

  Marker	Sensitivity	Specificity
  Calponin	Excellent	Very good
  p63	Excellent	Excellent
  Smooth muscle myosin heavy chain	Good	Excellent
  CD10 (CALLA)	Good	Good
  High molecular weight cytokeratin	Very good	Poor
  Maspin	Good	Poor
  S100	Good	Very poor
  Actin	Good	Very poor

• E-cadherin appears to be a sensitive marker of ductal differentiation vs lobular differentiation; its utility in borderline lesions is currently uncertain

• Immunologic markers useful for identification of breast carcinoma

	GCDFP15 (BRST2)	Estrogen Receptor	Progesterone Receptor	PAX8
Infiltrating ductal carcinoma	60-70%	75%	50-60%	0%
Infiltrating lobular carcinoma	60-70%	>95%	80%	0%
Lung adenocarcinoma	0-1%	<5%	<5%	0%
Ovarian adenocarcinoma	1-5%	50-100%	40-90%	90-100%
Endometrioid adenocarcinoma	negative	70%	70%
GI adenocarcinoma	negative	<5%	1-10%	0%
Pancreatic adenocarcinoma	negative	negative	0-5%	0%
Cholangiocarcinoma	negative	negative	30%
Thyroid carcinoma	negative	20%	30%	100%

• Sweat gland and salivary gland neoplasms may also be positive for GCDFP15, ER and PR
• Prostatic adenocarcinoma may be positive for GCDFP15

• CK7 and CK20 have not been tested on a series of histiocytoid carcinomas, thus their utility is unknown

  CK7 and CK20 expression in carcinomas
  CK7+20+	CK7-20+
  Ovary mucinous 90%	Colorectal adeno 80%
  Transitional cell 65%	Merkel cell 70%
  Pancreas adeno 65%	Gastric adeno 35%
  Cholangio 65%
  Gastric adeno 40%
  Excluded tumors 5% or less Carcinoid; Germ cell; Esoph squam; Head/neck squam; Hepato-cellular; Lung small cell & squam; Ovary non-mucinous; Renal adeno	Excluded tumors 5% or less Breast; Carcinoid lung; Cholangio; Esoph squam; Germ cell; Lung all types; Hepato-cellular; Ovary; Pancreas adeno; Renal adeno; Transitional cell; Uterus endometrioid
  CK7+20-	CK7-20-
  Ovary non-mucinous 100%	Adrenal 100%
  Thyroid (all 3 types) 100%	Seminoma & Yolk Sac 95%
  Breast 90%	Prostate 85%
  Lung adeno 90%	Hepatocellular 80%
  Uterus endometrioid 85%	Renal adeno 80%
  Embryonal 80%	Carcinoid intestinal & lung 80%
  Mesothelioma 65%	Lung small cell & squam 75%
  Transitional cell 35%	Esoph squam 70%
  Pancreas adeno 30%	Head/neck squam 70%
  Cholangio 30%	Mesothelioma 35%
  Excluded tumors 5% or less Colorectal adeno; Ovary mucinous; Yolk Sac; Seminoma	Excluded tumors 5% or less Breast; Cholangio; Lung adeno; Ovary; Pancreas adeno

• Derived from Chu PG, Weiss LM. Histopathology 2002, 40:403-439 and other sources

Prognostic/Therapeutic Markers

• Estrogen receptor (ER) and progesterone receptor (PR) are important markers for directing therapy and determining prognosis
  • Current consensus is that any level of positivity should be reported as positive
• Her2neu status can be determined by either immunohistology or by FISH
  • The other technique can be used for borderline case

Genetic analysis

• Her2neu status can be determined by either immunohistology or by FISH
  • The other technique can be used for cases borderline by one procedure

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