Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Quick Reference Handbook for Surgical Pathologists > Chapter 1: Immunostains - Introduction > Flashcards

Chapter 1: Immunostains - Introduction Flashcards

1
Q

Name some immunostains that can differentiate carcinomas/lymphomas/melanomas.

A

Carcinoma: Cytokeratins

Lymphoma: CD45

Melanoma: S100, MelanA, HMB45

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name some general prognostic markers.

Name some germane to breast cancer, and CLL.

A

Ki67 (MIB1) and p53

Her2 (adverse prognosis in breast cancer)

CD38 (adverse prognosis in CLL)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Name some predictive markers in breast and other cancers.

A

ER/PR (predicts tamoxifen response in breast)

Her2 (predicts trastuzumab response in breast)

c-Kit (predicts imatinib response in general)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why is p53 overexpressed in p53-mutated tumors?

A

Inactivating mutations in p53 also disable protein degradation, resulting in overexpression.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What types of antigens should be nuclear in localization?

A

Transcription factors (TTF-1, CDK2, Myogenin, WT1, p53), steroid hormone receptors (ER, PR), and Ki67 (except in hyalinizing trabecular adenoma of thyroid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What types of antigens should be cytoplasmic in localization?

A

The vast majority, including all intermediate filaments, contractile proteins, melanosome-associated proteins, secretory products, and other functional molecules.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What types of antigens should be membranous in localization?

A

Receptors, adhesion molecules, virtually all CD (cluster of differentiation) antigens. Be careful to distinguish from cytoplasmic, especially in Her2 & EGFR.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name some antigens that have characteristic combined nuclear and cytoplasmic reactivity.

A

S-100, calretinin, and beta-catenin (with mutations in APC pathway, eg deep fibromatosis and colon cancer.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is granular immunoreactivity indicate? Examples?

A

Localization to cytoplasmic organelles. For example, racemase (mitochondrial/peroxisomal), P501S (golgi), and Napsin A (lysosomal).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What does punctate immunoreactivity indicate? Example?

A

Represents some antigens that aggregate in the cytoplasm, eg CK tangles that form in neuroendocrine carcinomas.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name some examples in which loss of immunoreactivity is diagnostic.

A

DPC4 loss in pancreatic carcinoma

E-cadherin loss in lobular breast carcinoma

INI-1 loss in rhabdoid tumors and AT/RT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are cytokeratins classified and stratified?

A

Moll’s catalogue, in which they are separated based on gel electrophoresis.

CK1-8 are basic, CK9-20 are acidic.

CK1-6 and 9-17 are HMW, 7-8 and 18-20 are LMW.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Distinguish the distribution of HMWCKs, LMWCKs, and intermediate weight CKs.

A

HMWCKs: Expressed in squamous epithelia. Called “tonofilaments” ultrastructurally.

LMWCKs: Loosely distributed in the cytoplasm and unable to bundle. Found in visceral organs.

Intermediate: Usually 5, 6, and 17. Found in basal cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why are certain pairs of CKs expressed jointly? Name some examples.

A

Keratins are heterodimers consisting of an acidic and basic heterodimer. Classic pairs include 1+10 and 8+18.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What do the following cytokeratin cocktails detect?

  1. AE1
  2. AE3
  3. Cam5.2
  4. CK5/6
  5. CK903
A
  1. All acidic CKs except 9/12/17/18
  2. All basic cytokeratins (1-8)
  3. LMWCKs (8, 18)
  4. HMWCKs (5>6)
  5. HMWCKs (1, 5, 10, 14)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How are HMWCKs and LMWCKs differently expresses in carcinomas?

A

Squamous cell carcinomas express HMWCKs (but poorly-differentiated may co-express LMWCKs)

Adenocarcinomas and carcinoma of visceral epithelia express LMWCKs (but eg Pancreas, endometrium, breast, urothelial will co-express HWMCKs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What carcinomas will not stain AE1/AE3?

A

HCC (expresses CK18)

RCC (can be CK-negative in general)

Neuroendocrine carcinomas (variable, Cam5.2 is better?)

Adrenocortical neoplasms (often CK negative)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What roles do EMA, CEA, and p63 have in the context of cytokeratin IHC?

A

EMA and CEA can be thought of as “LMWCK-equivalents” in glandular epithelia, with p63 as a “HMWCK-equivalent” in squamous, urothelial, and basal cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What three classes of non-carcinomas can be cytokeratin positive?

A
  1. Tumors with true epithelial differentiation (eg epithelioid sarcomas, germ cell tumors, chordoma, mesothelioma)
  2. High-grade cancers with aberrant epithelial reactivity (usually focal, with Cam5.2)
  3. Gliomas and reactive astrocytes (may cross react with AE1/AE3).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How can Bowen’s disease (SqIS) be distinguished from Paget’s disease?

A

Paget’s is Cam5.2+ (LMWCK).

Bowen’s disease is CK903 (or CK5/6)+.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are some uses for CK903 and CK5/6?

A

Urothelial (CK903+) vs prostate (CK903-)
Mesothelioma (CK5/6+) vs adenocarcinoma (CK5/6-)
UDH (CK903+) vs DCIS (CK903-)

Identifying basal cells in prostatic lesions (CK903+)
Identifing metaplastic breast cancer (CK903+)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the utility of Ber-EP4?

A

Reacts with majority of adenocarcinomas. Mostly used to distinguish lung adenocarcinoma (+) from mesothelioma (-). Especially useful in cytology of effusions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which organs are CK7+, CK20-?

A

Above the diaphragm organs (lung & mesothelioma, breast, thyroid, salivary gland) and the gyne tract (uterus, non-mucinous ovary).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which organs are CK7-, CK20+?

A

Below the diaphragm GI tract (colorectal) and Merkel cell carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Which organs are CK7+, CK20+?
Peridiaphragmatic GI organs (**pancreaticobiliary, stomach**) and **bladder**, as well as **mucinous ovarian**.
26
Which organs are **CK7-, CK20-**?
Simple visceral epithelia (**liver, kidney, prostate**), **adrenal gland**.
27
Which tumors are **CK+, EMA-**?
HCC (CK18) Adrenocortical neoplasms (often CK- though) Most neuroendocrine neoplasms Embryonal carcinoma, yolk sac tumor Thyroid
28
Which tumors are **CK-, EMA+**?
Meningioma Perineurioma Plasma cell neoplasms, HL, ALCL RCC (sometimes)
29
What carcinomas are usually CEA+?
HCC (canalicular pattern with pCEA) Pancreaticobiliary Stomach Colorectum Lung adenocarcinoma
30
Recall some vimentin-positive carcinomas.
RCC (clear cell) Endometrium Mesothelioma Thyroid Salivary gland Sweat gland Spindle cell carcinomas in general
31
What is the application of vimentin IHC?
A mesencymal marker that is unfortunately too nonspecific for differentiating tumors. Mostly used to confirm tissue immunoviability when all other markers are negative.
32
1. Name two pan-muscle markers. 2. Name three skeletal muscle markers. 3. Name four smooth muscle & myoepithelial markers. 4. Which of the above in #3 are absent in myofibroblasts?
1. Desmin, muscle-specific actin (MSA) 2. MyoD, Myogenin, alpha-sarcomeric actin 3. SMA (alpha-actin), calponin, h-Caldesmon, SMMHC. 4. Myofibroblasts lack caldesmon and SMMHC. They may variably express calponin.
33
How do desmin and actins complement one another?
Usually, desmin staining pairs with actins. Actins are actually slightly more sensitive (may be positive in leiomyosarcomas). However, some tumors can unexpectedly be desmin+/actin- (desmoplastic small round cell tumor, Wilms tumor, mesothelial cells).
34
Summarize the main 5 neuroendocrine markers.
Synaptophysin: More sensitive (order with CHR) Chromogranin: More specific (order with SYN) NSE: Not actually specific (stains glial cells), so rarely used. CD56: Most sensitive, but usually not needed. CD57: Leu-7, sometimes a second-line marker.
35
What non-neuroendocrine tumors can stain SYN/CHR? Which are generally SYN+/CHR-?
Neoplasms of neuronal origin (eg Gangliocytoma) and PNETs. Adrenocortical neoplasms and pancreatic solid pseudopapillary tumor.
36
What role do peptide hormone stains serve in identification of neuroendocrine neoplasms?
They may help establish identity, but many cases can be nonfunctional or have ectopic hormone expression. Be cautious with occult neuroendocrine tumors.
37
What roles do cytokeratins play in neuroendocrine tumors?
Epithelial neuroendocrine tumors (carcinoid, pancreatic tumors, SCLC) are often CK-positive. Usually Cam5.2, but also get AE1/AE3. High grade NE carcinomas have punctate perinuclear CK staining.
38
Summarize the main four markers of melanocytic differentiation.
**MelanA/Mart1**: Stains almost all epithelioid melanomas, and few/no spindled or desmoplastic. Also stains steroid hormone producers. **HMB45**: Like Melan-A, but more specific (does not stain steroid hormon producers). Also does not stain *mature* melanocytes. **S100**: Stains nearly all melanomas. Very nonspecific. **MITF**: Nuclear, somewhat specific. Kind of meh.
39
Besides melanomas, what other tumors will stain melanosomal markers?
Clear cell sarcoma/melanoma of soft parts, melanotic neurofibroma, melanotic schwannoma, and PEComas (AML, LAM, pulmonary sugar tumor).
40
What role do the markers **SOX10, PNL2,** and **MUM1** play?
They are newer melanocytic makers that identify epithelioid but not spindle cell melanoma.
41
In addition to typical neuroendocrine markers, what markers will stain neurons?
**Neurofilament** (axonal) **NeuN** (nuclear)
42
What utility is offered by **GFAP**?
Stains glial cells (astrocytes, oligodendrocytes, ependymal cells, and some schwann cells) to distinguish gliomas from non-glial tumors and inflammatory conditions.
43
What markers can identify schwann cells?
S-100 (first line) CD57, GFAP (second line)
44
Summarize 5-6 vascular markers.
**CD34**: Lots of cross-reactivity (see other card) **CD31**: More sensitive and specific? **Factor VIII**: Actually vWF. **Ulex europaeus I** **FLI-1, ERG**: Nuclear?
45
Recall some CD34+ non-vascular tumors.
Solitary fibrous tumor Dermatofibrosarcoma protuberans Gastrointestinal stromal tumor Epithelioid sarcoma Nerve sheath tumors Granulocytic sarcoma
46
What markers can be useful in the assessment of invasion in prostate and breast cancers?
Prostate: **CK903** (cytoplasmic) and **p63** (nuclear) mark basal cells. They are absent in invasion, and the invasive acinar cells should express **racemase**. Breast: **SMA, SMMHC, Calponin, p63, S100, C10** should all stain myoepithelial cells, which are absent in invasion.
47
1. Do carcinomas normally express S-100? 2. Do spindle cell and desmoplastic melanomas stain S-100? Do pheochromocytoma/paraganglioma stain S-100?
1. No, but 30% of breast cancers do. 2. Yes, but they may not express MelanA/HMB45. 3. S-100 reactivity is present in sustentacular (supporting) cells.
48
What hematopoietic neoplasms do not express CD45?
Lymphoblastic lymphoma (variable) Anaplastic large cell lymphoma (variable) Classical HL Plasma cell neoplasms Follicular dendritic cell sarcoma Myeloid sarcoma (variable)
49
Name some site specific markers of **breast**.
ER/PR (60%) GCDFP-15 (50%) Mammaglobin (50%) (Her2 is not specific!)
50
Name some site specific markers of **prostate**.
PSA, PSAP Prostein (P501S) PSMA
51
Name some site specific markers of **lung**
TTF-1 (75% of non-mucinous adenocarcinomas, 90% of SCLCs) Napsin A Surfactant (PE10)
52
Name some site specific markers of **thyroid** (Papillary/follicular vs medullary!).
Papillary/follicular: TTF-1, thyroglobulin, PAX8 Medullary: TTF-1, calcitonin
53
Name some site specific markers of **liver**
HepPar-1 Canalicular CD10
54
Name some site specific markers of **pancreas**
Loss of DPC4 expression (55% of adenocarcinomas)
55
Name some site specific markers of **kidney**.
PAX2 PAX8 CAIX
56
Name some site specific markers of **adrenal gland**.
Inhibin | (melan-A is not very specific)
57
Name some site specific markers of **Gyne tract**.
Pax8 ER/PR (100% of endometrioid, 50% of serous, 0% of cervical) WT1 (serous carcinomas)
58
Name some site specific markers of **pituitary, parathyroid, and pancreatic islet**.
Pituitary: Prolactin, GH, FSH/LH, TSH, ACTH Parathyroid: PTH Pancreatic islet: Glucagon, insulin, somatostatin
59
Name some site specific markers of **bladder**.
p63 Uroplakin GATA3 (thrombomodulin is less specific)
60
Name some site specific markers of **intestine, gallbladder, and stomach**.
Intestine: CDX2, villin Gallbladder/stomach: (no specific markers available).
61
Name some site specific markers of squamous cell cancers of cervix, anus, and tonsil.
**HPV** (ISH) ## Footnote **p16**
62
Recite a differential diagnosis for small round cell blue cell tumors of childhood, and what stains would be useful.
Lymphoblastic lymphoma (CD45, CD34, CD99) Rhabdomyosarcoma (desmin) Wilms tumor (WT1) PNET/Ewing (CD99, NE markers) Neuroblastoma (Phox2B) Medulloblastoma (NE markers, GFAP variable) Small cell osteosarcoma (CD99 variable, osteocalcin)
63
Recite a differential diagnosis for small round blue cell tumors of adulthood, and some useful stains.
Lymphoma (CD45) Small cell carcinoma (CK, NE markers, TTF1 variable) Merkel cell carcinoma (CK7/20, NE markers) Desmoplastic small round cell tumor (CK, WT1, desmin) Mesenchymal chondrosarcoma (CD99, Sox9)
64
Recite some categories of tumor differentiation that should be considered in spindle cell tumors, and what markers can define them.
Muscle (Desmin) Nerve sheath (S100, CD34) Vascular (CD34) Myofibroblastic (SMA) Fibrohistiocytic (CD34?) Adipose (S100) Spindle carcinomas (CK) Others: GIST, SFT, synovial sarcoma...
65
In what contexts is ER/PR staining considered uninterpretable? Negative?
Internal control issue fails to stain, or specimen handling did not conform to requirements (6-72hrs fixation in 10% NBF) Negative only if \<1% staining with appropriately staining internal control.
66
How is Her2 Dako HercepTest IHC scored?
0 = \<30% staining 1+ = \>30%, partial membrane staining 2+ = \>30%, weak but complete membrane staining 3+ = \>30%, strong complete membrane staining.
67
How is Her2 FISH scored?
Her2 amplified: \>6 HER2 copies per nucleus or ratio of FISH signals to chr17 \> 2.2 Her2 non-amplified: \<4.0 Her2 gene copies per nucleus or FISH ratio \< 1.8
68
How is EGFR PharmDx assay interpreted?
0 = no staining 1+ = \>1%, weak membranous 2+ = \>1%, moderate membranous 3+ = \>1%, strong membranous

Quick Reference Handbook for Surgical Pathologists (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions