Stains Flashcards

1
Q

Expression of CK 5/6

A

Expression of CK 5/6

  • Mesothelioma
  • Squamous/Basal Cell Carcinoma
  • Salivary Gland Tumor
  • Breast
  • Skin Adnexa
  • Urothelial Carcinoma
  • Thymoma
  • Endocervical Adenocarcinoma
  • Synovial Sarcoma (+/-)
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2
Q

TFE3

A

TFE3

  • Alveolar Soft Part Sarcoma (98%)
  • Renal Cell Carcinoma With Xp11.2 Translocation (97%)
  • Renal Cell Carcinoma t(X;1)(p11;q21) (76%)
  • Epithelioid Hemangioendothelioma (75%)
  • Granular Cell Tumor (68%)
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3
Q

EPITHELIAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN

A

EPITHELIAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN

  • Thyroid Carcinoma
  • Endometrial Carcinoma
  • Renal Cell Carcinoma
  • Mesothelioma
  • Myoepithelial Carcinoma
  • Metaplastic Breast Carcinoma
  • Sarcomatoid Carcinoma
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4
Q

MESENCHYMAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN

A

MESENCHYMAL TUMORS THAT COEXPRESS CYTOKERATIN AND VIMENTIN

  • Synovial Sarcoma
  • Epithelioid Sarcoma
  • Epithelioid Angiosarcoma
  • Desmoplastic Small Round Cell Tumor
  • Leiomyosarcoma
  • Malignant Rhabdoid Tumor
  • Chordoma
  • Adamantinoma
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5
Q

BREAST DIRECTED IMMUNOMARKERS

A

BREAST DIRECTED IMMUNOMARKERS

  • GROSS CYSTIC DISEASE FLUID PROTEIN 15 (GCDFP15)
  • MAMMAGLOBIN
  • NYBR 1
  • GATA 3
  • TFF 1
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6
Q

GATA3

A

GATA3 (nuclear)

  • Breast carcinoma
  • Urothelial carcinoma
  • Cutaneous Basal cell carcinoma
  • Cutaneous squamous carcinoma
  • Trophoblastic tumors
  • Endodermal sinus tumor
  • Chromophobe renal cell carcinoma
  • Pancreatic ductal adenocarcinoma
  • Salivary gland ductal carcinoma
  • Paraganglioma
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7
Q

ER Positive Tumors

A

ER Positive Tumors

  • Breast
  • Ovarian
  • Endometrial
  • Lung
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8
Q

PANEL OF IMMUNOMARKERS FOR THE DISTINCTION OF CK7+/ER+TUMORS

A

PANEL OF IMMUNOMARKERS FOR THE DISTINCTION OF CK7+/ER+TUMORS

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9
Q

GASTRO-INTESTINAL TRACT DIRECTED IMMUNOMARKERS

A

GASTRO-INTESTINAL TRACT DIRECTED IMMUNOMARKERS

  • CDX2
  • SATB2 (colon)
  • CDH17
  • CK17
  • Villin
  • EMERGING MARKER: LEF1
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10
Q

SATB2

A

SATB2

  • Nuclear matrix – associated transcription factor and epigenetic regulator
  • Positive in small bowel and colon adenocarcinoma
  • Positive in lower GI neuroendocrine
  • Expressed in majority of colorectal tumors including most poorly differentiated tumors
  • Negative in upper GI and pancreatic tumors
  • Ovarian, breast and lung adenocarinoma low
  • Sensitive marker of osteoblastic differentiation
  • Special AT-rich sequence binding protein 2
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11
Q

CADHERIN-17 (CDH 17) LIVER-INTESTINE CADHERIN

A

CADHERIN-17 (CDH 17) LIVER-INTESTINE CADHERIN

  • Calcium-dependent transmembrane glycoprotein
  • Mediates cell – cell adhesion and acts as intestinal peptide transporter
  • Expressed in normal glandular epithelium of GI tract and normal pancreatic ducts
  • Normal Colon/Small Intestine (100%)
  • Adenocarcinoma, Colon/Rectum (98%)
  • Lymphoepithelioma-like Carcinoma, Colon/Rectum (89%)
  • Adenoma, Metanephric (81%)
  • Adenocarcinoma, Bladder (70%)
  • Adenocarcinoma, Esophageal (67%)
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12
Q

LEF-1 EXPRESSION

A

LEF-1 EXPRESSION IN COLORECTAL TUMORS

  • LEF-1 is a TCF genes, activator (Lymphoid enhancer factor – 1/T cell factor)
  • LEF-1 is a DNA binding protein that interacts with β catenin and activates Wnt–responsive target genes
  • a/w KRAS mutation
  • Pancreatoblastoma (100%)
  • Solid Pseudo Papillary Tumor, Pancreas (100%)
  • CLL/SLL (89%)
  • Squamous Cell Carcinoma, Oropharynx (63%)
  • Adenocarcinoma, Colon/Rectum (37%)
  • DLBCL, Richter Transformation (21%)
  • DLBCL, NOS (16%)
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13
Q

IMMUNOMARKERS FOR GASTROINTESTINAL

TUMORS

A

IMMUNOMARKERS FOR GASTROINTESTINAL

TUMORS

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14
Q

PANCREATIC MARKERS

A

PANCREATIC MARKERS

  • CK17:
    • Low molecular weight Cytokeratin – myoepithelial cell and basal cells
    • Pancreatic DADC + 60%
  • S100P:
    • Belongs to the family S100 calcium binding protein
    • 95 amino acid protein purified from human placenta
    • Pancreatic DADC + 90%
  • Maspin :
    • (Serpin B5) Tumor supressor gene
    • Pancreatic DADC - +
  • pVHL (Von Hippel – Lindau)
    • Tumor Supervisor gene
    • Pancreatic DADC - +
  • IMP3:
    • Oncofetal RNA – binding protein
    • Pancreatic DADC - +
  • MUC5 AC:
    • High molecular weight Glycoprotein of mucin family
    • Pancreatic DADC +
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15
Q

DISTINCTION OF PANCREATIC DUCTAL

ADENOCARCINOMA FROM CHRONIC PANCREATITIS

A

DISTINCTION OF PANCREATIC DUCTAL

ADENOCARCINOMA FROM CHRONIC PANCREATITIS

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16
Q

LIVER DIRECTED IMMUNOMARKERS

A

LIVER DIRECTED IMMUNOMARKERS

  • Hep PAR1
  • GLYPICAN -3
  • ARGINASE 1
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17
Q

HEPATOCELLULAR CARCINOMA MARKERS

A

HEPATOCELLULAR CARCINOMA

  • Glypican - 3
  • HePAR 1
  • Arginase -1
  • Alpha feto protein
  • CDIO
  • pCEA
  • CD 34
  • Glutamine Synthetase
  • Heat shock protein 70
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18
Q

ANTIBODIES TO IDENTIFY

HEPATOCELLULAR DIFFERENTIATION

A

ANTIBODIES TO IDENTIFY

HEPATOCELLULAR DIFFERENTIATION

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19
Q

IMMUNOMARKERS FOR CONFIRMING

HEPATOCELLULAR DIFFERENTIATION

A

IMMUNOMARKERS FOR CONFIRMING

HEPATOCELLULAR DIFFERENTIATION

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20
Q

DISTINCTION OF CHOLANGIOCARCINOMA FROM METASTATIC TUMORS

A

DISTINCTION OF CHOLANGIOCARCINOMA FROM METASTATIC TUMORS

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21
Q

Metastatic Prostate Carcinoma Markers

A

Metastatic Prostate Carcinoma

  • PSA
  • PAP
  • Prostein
  • NKX.3
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22
Q

What do these stain in addition to prostate?

  • PSA
  • PAP
  • NKX3.1
A

What do these stain in addition to prostate?

  • PSA:
    • Salivary gland tumors
    • Bladder adenocarcinoma
    • Periurethral glands
    • Melanoma
    • Anal glands
    • Urachal remanants
  • PAP
    • NE Tumors
  • NKX3.1
    • Lobular Carcinoma Breast
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23
Q

Urothelial Carcinoma Markers

A

Urothelial Carcinoma

  • Uroplakin III
  • Thrombomodulin
  • GATA-3
  • CK7+/CK20+, CK5/6, p63
  • Emerging markers: S100P, Uroplakin II
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24
Q

KIDNEY – DIRECTED ANTIBODIES

A

KIDNEY – DIRECTED ANTIBODIES

  • PAX2/PAX8
  • RCC Ma
  • CD10
  • CA IX
  • AMACR
  • cKIT
  • CATHEPSIN
25
Q

ADRENAL GLAND DIRECTED IMMUNOMARKERS

A

ADRENAL GLAND DIRECTED IMMUNOMARKERS

  • INHIBIN ALPHA
  • MELAN A (A103)
  • CALRETININ
  • Steroidogenic factor 1 (SF-1)
26
Q

MESOTHELIUM – DIRECTED ANTIBODIES

A

MESOTHELIUM – DIRECTED ANTIBODIES

  • Calretinin
  • Cytokeratin 5 or 5/6
  • Podoplanin (D2-40)
  • WT-1 (also serous carcinoma)
  • Thrombomodulin
  • Mesothelin
27
Q

CALRETININ

A

CALRETININ - cytoplasm

  • Mesothelial cells/Mesothelioma
  • Sex cord-stromal neoplasms
  • Adrenocortical Cells
  • up to 38% of Adenocarcinoma
28
Q

PODOPLANIN (D2-40)

A

PODOPLANIN (D2-40) - membranous

Trans-membrane mucoprotein

  • Mesothelial cells/Mesothelioma
  • Lymphatic endothelium
  • Lymphangiomas
  • Kaposi sarcomas
  • Angiosarcoma (subset)
  • Seminomas
  • Epithelioid mesotheliomas
29
Q

MESOTHELIN

A

MESOTHELIN

  • Mesothelial
  • Pancreatic Adenocarcinoma
  • Ovarian Serous Ca
  • Urothelial carcinoma
  • Lung Adenocarcinoma
  • Lung Squamous cell +/-
30
Q

ANTIBODIES DIRECTED AGAINST CARCINOMA

A

ANTIBODIES DIRECTED AGAINST CARCINOMA

  • MOC 31
  • Claudin -4
  • BerEP4
  • CEA
  • TAG – 72 (B72.3)
  • BG – 8
  • CD - 15
31
Q

DISTINCTION OF BENIGN MESOTHELIAL CELLS FROM MESOTHELIOMA

A
32
Q

Neuroendocrine Markers

A

Neuroendocrine Markers

  • CD56
  • Synaptophysin
  • Chromogranins
  • PAX5
33
Q

METASTATIC MERKEL CELL CARCINOMA MERKEL CELL CARCINOMA

A

METASTATIC MERKEL CELL CARCINOMA MERKEL CELL CARCINOMA

  • CK20
  • NF
  • Merkel cell polyoma virus (oncovirus)
34
Q

MELANOMA MARKERS

A

MELANOMA MARKERS

  • S-100
  • HMB45
  • MART-1
  • Tyrosinase
  • SOX10
  • PNL2

DESMOPLASTIC MELANOMA

  • S100
  • SOX10
35
Q

CLEAR CELL RENAL CELL CARCINOMA

A

CLEAR CELL RENAL CELL CARCINOMA

  • POSITIVE MARKERS
    • AE1/AE3
    • EMA
    • RCC m
    • PAX2/PAX8
    • Vimentin
    • CD10
    • Carbonic anhydrase IX
  • NEGATIVE MARKERS
    • CK7
    • CD117
    • Ksp-cadherin
36
Q

PAPILLARY RENAL CELL CARCINOMA

A

PAPILLARY RENAL CELL CARCINOMA

  • Positive Markers:
    • Keratin
    • Vimentin
    • RCC Ma
    • Rasimase
    • CK7
    • Pax2/Pax8
    • CD10 (67-93%)
  • Negative Markers:
    • CA IX
    • Cathepsin K
    • TFE3/TFEB
    • CD117
37
Q

CHROMOPHOBE RENAL CELL CARCINOMA

A

CHROMOPHOBE RENAL CELL CARCINOMA

  • POSITIVE MARKERS
    • CK7
    • CD117
    • PAX2/PAX8
    • Ksp CADHERIN
  • NEGATIVE MARKERS
    • VIMENTIN
    • CD10
    • RCC Ma
    • CA IX
38
Q

RENAL ONCOCYTOMA

A

RENAL ONCOCYTOMA

  • POSITIVE MARKERS
    • CD117
    • Ksp Cadherin
    • PAX8
    • AE1/AE3
  • NEGATIVE MARKERS
    • CK7
    • Vimentin
    • CA IX
    • CD10
    • RCCm
39
Q

COLLECTING DUCT CARCINOMA

A

COLLECTING DUCT CARCINOMA

  • POSITIVE
    • CK7
    • CEA
    • 34βE12
    • Ulex Europeus
    • PAX8
  • NEGATIVE
    • CK20
    • CD10
    • AMACR
    • CA IX
    • P63
    • GATA 3
40
Q

DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS CLEAR CELLS

A

DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS CLEAR CELLS

41
Q

DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS WITH A PAPILLARY COMPONENT

A
42
Q

DIFFERENTIAL DIAGNOSIS OF RENAL TUMORS WITH ONCOCYTIC FEATURES

A
43
Q

DIFFERENTIAL DIAGNOSIS OF DISTAL NEPHRON-LIKE CARCINOMAS

A
44
Q

Vascular tumor markers

A

Vascular tumor markers

  • CD31 - good for dermal vascular stain BUT histiocytes will stain granular positive
  • Erg - better marker, nuclear marker
45
Q

Spindle Cell DDx Markers

A
46
Q

CK7/CK20 negative?

A

CK7/CK20 negative

  • Prostate
  • Kidney
  • Liver
  • Adrenal Gland Ca
  • Germ Cell: Seminoma & Yolk Sac
  • Squamous cell carcinoma
47
Q

CK7/CK20 Positive?

A

CK7/CK20 Positive

  • Ovary- Mucinous carcinoma (90%)
  • Bladder- Urothelial carcinoma (65-89%)
  • Pancreas- Adenocarcinoma (65%)
  • Bile Duct- Cholangiocarcinoma (65%)
  • Stomach- Adenocarcinoma (38-40%)
  • Excludes: Carcinoid, Esophageal Squamous Ca, Head/Neck Squamous Ca, Liver Hepatocellular Ca, Lung Small Cell & Squamous Ca, Ovarian NonMucinous Ca, Kidney Renal Cell Ca
48
Q

CK7+/CK20-

A

CK7+/CK20-

  • Lung- Adenocarcinoma (72-90%)
  • Ovary- Non-Mucinous Ca (100%)
  • Thyroid- all types (90%)
  • Breast- Ductal & Lobular Ca (80-90%)
  • Uterus- Endometrial carcinoma (80-85%)
  • Germ Cell- Embryonal Ca (80%)
  • Pleura- Mesothelioma (65-69%)
  • Bladder- Urothelial (35%)
  • Kidney- Renal cell carcinoma (24%)
  • Pancreas- Adenocarcinoma (26-30%)
  • Bile Duct- CholangioCa (30%)
  • Breast- Mucinous Carcinomas
  • Excludes: Colorectal Ca, Ovary Mucinous Ca, Seminoma, Yolk Sac Tumor
49
Q

CK7-/CK20+

A

CK7-/CK20+

  • Colorectal - Adenocarcinoma (75-80%)
  • Skin- Merkel Cell Carcinoma (70%)
  • Stomach- Gastric Adenocarcinoma (35%)
  • Colorectal- Mucinous Carcinomas
  • Excludes: Breast Ca, Carcinoid, CholangioCa, Esophageal Squamous, Germ cell, Lung (all types), Liver Hepatocellular Ca, Ovarian Ca, Pancreas Ca, Kidney Renal Ca, Bladder Urothelial Ca, Uterus Endometrioid
50
Q

Mucinous Tumor Subsets - Staining Pattern

  • Breast
  • Colorectal
  • Ovary
A

Mucinous Tumor Subsets - Staining Pattern

  • Breast
    • CK 7 + CK20 -
  • Colorectal
    • CK7 - CK20 +
  • Ovary
    • CK7 + CK20 +
51
Q

IMP3

A

IMP3

  • Decidua (100%)
  • Normal Trophoblasts (100%)
  • Pancreas: Adenocarcinoma, Papillary (>90%), PIN (57%)
  • Esophagus: Barrett’s, Adenocarcinoma (>90%)
  • Endocervical AIS (93%)
  • Uterine/Endometrial: Papillary serous adenocarcinoma (99%), Clear Cell Carcinoma (61%)
  • Ovarian Serous Cystadenocarcinoma (68%)
  • Melanoma (85-90%)
  • Cholangiocarcinoma, Intrahepatic (85%)
  • Adenoid Cystic Carcinoma (81%)
  • Mesothelioma (74%)
  • Lung Adenocarcinoma (55%)
52
Q

Ovarian Serous Carcinoma

A

Ovarian Serous Carcinoma

Mesothelin

53
Q

GRANULOSA CELL TUMOR, stains

A

GRANULOSA CELL TUMOR

  • Inhibin
  • Calretinin
  • Vimentin
  • WT1
  • CD 99
  • S100
  • CD56
  • SF1 (steroidogenic factor)
  • FOXL2 gene abnormality on xsome 3
54
Q

Breast Panel

A

Breast Panel

Invasion?

Myoepithelial (basal): + (HMW) CK5/6, CK14 (lg ducts only), CK17, p63, S100, actin, calponin, SMA, myosin heavy chain, CD10

Luminal: + (LMW) CK7,8,18,19

Basal lamina: type IV collagen, laminin

UDH: + ER (heterogenous), + CK5/6 (mosaic pattern)

ADH/low-grade DCIS: + ER (strong, uniform), - CK5/6 (Neg in neoplastic cells, only + in surrounging myoepithelial cells)

High-grade DCIS: + HER2 (strong membranous), +p53

DCIS: p120 catenin (membranous)

LCIS: + ER (strong, diffuse), - HER2 (+pleomorphic), - p53(+pleomorphic), - E-cadherin, + p120 catenin (cytoplasmic)

Metaplastic/Spindle cell carcinoma: + HMW (variable), CK5/6, 34betaE12, +p63, +vimentin, +SMA, triple negative, +myoep/basal, “claudin low”

Fibromatosis: +Beta-catenin (nuclear, can be seen in phyllodes stroma and metaplastic), +actin, +/-desmin, +/-S100 (minority of cells)

55
Q

Endometriod Endometrial Adenocarcinoma

A

Endometriod Endometrial Adenocarcinoma

  • Positive: CK/EMA (undifferentiated focally +), ER, PR (+/- in high grade), pax-8, vimentin, WT1 (variable), Mammoglobin (~ 50%), (squamous areas + p16, p63, and CD10)
  • Negative: p53, p16 (-/patchy, +/- diffusely positive in high grade), HNF-1-β, Napsin-A (+ in secretory variant)

Mismatch repair testing

  • MLH1/PMS2/MSH2/MSH6 intact staining: Unlikely germline mutation (< 5%)
  • MSH2/MSH6 loss: Indicative of germline mutation, genetic counseling recommended
  • MLH/PMS2 loss: Recommend MLH1 promoter methylation testing
  • If hypermethylated, likely represents sporadic inactivation rather than germline mutation
  • If not hypermethylated, genetic counseling recommended as patient likely carries a germline mutation in MLH1
56
Q

Serous Endometrial Adenocarcinoma

A

Serous Endometrial Adenocarcinoma

Positive: p53 and p16 (diffuse/strong + or completely negative), pax-8, IMP2, IMP3, HMGA2 (frequently), Ki-67 >75%, WT1 positive in up to 1/3, +/- HER2, +/-D2-40, +/-HNF-1-β

Negative: ER, PR, Vimentin +/-

57
Q

Clear Cell Endometrial Adenocarcinoma

A

Clear Cell Endometrial Adenocarcinoma

Positive: HNF-1, High Ki-67, WT1/p16 (+ in ~ 1/3), C-erb-B2

Negative: ER, PR, p53, Cyclin-D1, E-cadherin

58
Q

Endometrial Stromal Sarcoma, High Grade

A

Endometrial Stromal Sarcoma, High Grade

High-grade component

  • CD10, ER, and PR typically negative
  • Cyclin-D1 diffusely and strongly positive
  • CD117 often positive but DOG1 negative
  • β-catenin may be positive

Low-grade component

  • CD10, ER, and PR positive
  • Cyclin-D1 may show patchy positive, but CD117 negative

Cytogenetics

  • t(10;17) with YWHAE-FAM22
  • Molecular Genetics
  • No KIT mutations