Introduction and Application of Fine Needle Aspiration Biopsy

, Jun Zhang² and Haiyan Liu¹

(1)

Department of Laboratory Medicine, Geisinger Health System, Danville, PA, USA

(2)

Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA

Keywords

SensitivitySpecificitySpindle cellsEpithelioid cellsSmall round cellsGiant cellsIntranuclear inclusionNuclear groovesParotid glandBenign mixed tumorAdenoid cystic carcinomaLiverHepatocellular carcinomaDuctal carcinomaPancreasBreastLobular carcinomaAdenocarcinomaLungSquamous cell carcinomaRenal cell carcinomaHodgkin’s lymphomaLymphomaSarcomaMelanomaGerm cell tumorMesotheliomaLangerhans cell histiocytosisGranular cell tumorPapillary thyroid carcinomaThyroid medullary carcinomaColloid carcinomaOncocytomaAcinar cell carcinomaNeuroendocrine tumorSmall-cell carcinoma Merkel cell carcinoma Fine-needle aspiration biopsyIn-situ hybridizationPolymerase chain reactionReverse transcription-polymerase chain reaction (RT-PCR ) Southern blotting Gene microarraysGenomicsHER2/neu for gene amplification in breast and gastric cancerDetection of clonality in hematopoietic neoplasmsSpecific chromosomal translocations CK7 CK20 AE1/3 CAM5.2 EMA Vimenti n MOC31 BerEP4 CEA Calretini n WT-1 CK5/6 D2-40 p40 p63 S100 CD10 Napsin A ER GATA3 PAX8 CDX2 SATB2 PSA NKX3.1 P504S PSAP pVHL RCC Chromograni n SOX10 Mart-1 HMB45 SALL4 OCT4 CD30Glypican-3CD117NKX2.2STAT6CD99MyogeninMyoD1DesminSMA

Indications for Fine Needle Aspiration (FNA) Biopsy

Mass lesion with a clinical suspicion of malignant tumor – palpable or deep-seated
Infections – virus, fungus
Granulomatous inflammation
Infiltration – amyloidosis

Complications of FNA

Pain
Bleeding
Faintness
Hematoma
Pneumothorax
Seeding of tumor cells

Advantages of FNA

FNA is SAFE.
- Simple
- Accurate
- Fast
- Economic

Primary Applications of FNA

Primary diagnosis of a malignant tumor.
Confirm a reactive/benign condition.
Metastatic tumor of unknown primary.
Deep-seated organ/tumor.
Confirm a recurrent tumor .

Target Organs of FNA

Superficial Organs

Thyroid
Lymph node
Salivary gland
Soft tissue
Breast

Deep-Seated Organs

Liver
Pancreas
Lung/mediastinum
Kidney/adrenal
Retroperitoneum

Sensitivity and Specificity of FNA (Table 1.1)

Table 1.1

Summary of sensitivity and specificity of FNA

Organ	Sensitivity (%)	Specificity (%)
Thyroid	83	92
Breast	92.5	99.8
Salivary gland	90	95
Lymph node	90	98
Lung	89	96
Liver	85	100
Pancreas	90	100
Kidney	85	98
Adrenal gland	85	100
Soft tissue	96	96

Note: When a sample is adequate for evaluation

How to Perform an FNA

Supplies

23- or 25-gauge, 1.0-inch or 1.5-inch needle
Syringes – 10 mL
Syringe holder (Fig. 1.1)

Fig. 1.1

Showing an aspiration gun (Cameco AB, Tägy, Sweden)

Procedure

Stabilize the target lesion.
Pass needle through the skin and advance into the lesion.
Apply suction.
Move the needle back and forth for 10 s.
Release suction.
Remove the needle from patient.
Detach the needle from the syringe.
Fill the syringe with air and replace needle on syringe.
Express the specimen onto microscopic slides.
Prepare air-dried and fixed smears .

How to Interpret an FNA

Overall Cellularity

High – lymphoma , melanoma , neuroendocrine tumor (NET ) (Fig. 1.2)

Fig. 1.2

Hypercellularity in melanoma
Low – lobular carcinoma , schwannoma (Fig. 1.3)

Fig. 1.3

Low cellularity in breast lobular carcinoma

Cellular Architectures

Papillary (Fig. 1.4)

Fig. 1.4

Papillary structure in papillary RCC
Tightly cohesive groups (Fig. 1.5)

Fig. 1.5

Cohesive cellular group in medullary carcinoma of the breast
Loosely cohesive groups (Fig. 1.6)

Fig. 1.6

Loosely cohesive group in breast carcinoma
Acinar (Fig. 1.7)

Fig. 1.7

Acinar formation in acinar cell carcinoma of the pancreas
Glandular (Fig. 1.8)

Fig. 1.8

Glandular formation in colonic ADC

Cell Shapes

Epithelial (Fig. 1.9)

Fig. 1.9

Epithelial cells in well-differentiated ADC of the pancreas
Epithelioid (Fig. 1.10)

Fig. 1.10

Epithelioid cells in melanoma
Spindle (Fig. 1.11)

Fig. 1.11

Spindle cell in gastrointestinal stromal tumor
Bizarre
Small round cell (Fig. 1.12)

Fig. 1.12

Small blue cell in Ewing’s sarcoma
Giant cell (Fig. 1.13)

Fig. 1.13

Giant tumor cells in rhabdomyosarcoma on Diff-Quik (DQ)

Naked Nuclei

Hepatocellular carcinoma (HCC) (Fig. 1.14)

Fig. 1.14

Naked nuclei in HCC
Acinar cell carcinoma
Granular cell tumor
Lactating adenoma
Fibroadenoma

Nuclear Details

Intranuclear inclusion – melanoma (Fig. 1.15), renal cell carcinoma (RCC ), papillary thyroid carcinoma , HCC, and paraganglioma

Fig. 1.15

Intranuclear inclusion in a melanoma
Nuclear grooves – papillary thyroid carcinoma , adult granulosa cell tumor, histiocytosis X (Fig. 1.16), solid-pseudopapillary tumor of pancreas

Fig. 1.16

Nuclear grooves in Langerhans cell histiocytosis
Anisonucleosis – high-grade neoplasms (Figs. 1.17 and 1.18)

Fig. 1.17

Nuclear pleomorphism in a melanoma

Fig. 1.18

Anaplastic carcinoma of the thyroid with marked nuclear pleomorphism
Nuclear chromatin clearing – pancreatic carcinoma
Prominent nucleoli – melanoma , high-grade lymphoma, HCC, high-grade RCC , adenocarcinoma (ADC) , and sarcoma

Cytoplasm

Clear – clear cell RCC (Fig. 1.19), clear cell carcinoma of the ovary and the uterus, melanoma , ADC with clear cell changes (such as pancreas), and squamous cell carcinoma (SCC) with clear cell changes

Fig. 1.19

Clear cytoplasm in a clear cell RCC
Granular – oncocytoma (Fig. 1.20), HCC, granular cell tumor (Fig. 1.21), high-grade RCC , medullary carcinoma of the thyroid, and other NETs/carcinomas

Fig. 1.20

Oncocytic cytoplasm in an oncocytoma

Fig. 1.21

Coarse, granular cytoplasm in a granular cell tumor
Foamy – RCC , carcinoma of the breast, lung, and pancreas, melanoma
Squamoid/dense – SCC (Figs. 1.22 and 1.23) , papillary thyroid carcinoma , carcinoma of the lung and pancreas, and high-grade mucoepidermoid carcinoma

Fig. 1.22

Squamous tumor cell in a SCC on DQ

Fig. 1.23

Keratinizing squamous tumor cell in an SCC on Papanicolaou (Pap) stain
Intracytoplasmic lumen – lobular carcinoma and low-grade ductal carcinoma of the breast (Fig. 1.24), signet-ring cell carcinoma, and melanoma

Fig. 1.24

Intracytoplasmic lumen in a breast lobular carcinoma

Background Material

Abundant mucin – colloid carcinoma of breast and pancreas (Figs. 1.25 and 1.26) and mucoepidermoid carcinoma

Fig. 1.25

Mucinous background in a colloid carcinoma of the breast on DQ

Fig. 1.26

Mucinous background in a colloid carcinoma of the breast on Pap stain
Abundant colloid – thyroid nodular goiter
Myxoid/chondroid – benign mixed tumor , chondrosarcoma, and myxoid and chondroid neoplasms (Figs. 1.27 and 1.28)

Fig. 1.27

Chondroid background in a chodorma on DQ

Fig. 1.28

Chondroid background in a chodorma on Pap stain
Amyloid – medullary carcinoma of the thyroid, NET , and endocrine tumor of the pancreas
Necrosis – colorectal ADC, small-cell undifferentiated carcinoma, lymphoma , and high-grade carcinoma or sarcoma
Crushed artifact – small blue cell tumor, lymphoma , and lymphoid tissue
Acute inflammation – infection, inflammatory process, anaplastic carcinoma of the thyroid, anaplastic large-cell lymphoma, and SCC with cystic degeneration

Single Cell Population

NET (Figs. 1.29)

Fig. 1.29

Single cell population in a carcinoid tumor of lung on DQ
Lymphoma /plasmacytoma/myeloid sarcoma (Fig. 1.30)

Fig. 1.30

Single cell population in a plasmacytoma on Pap stain
Melanoma
Sarcoma

Two Populations of Cells

Seminoma (Figs. 1.31 and 1.32)

Fig. 1.31

Two populations of cells in a seminoma on DQ

Fig. 1.32

Two populations of cells in a Hodgkin’s lymphoma on DQ
Thymoma
Hodgkin’s lymphoma (Fig. 1.32)
Lymphoepithelial carcinoma
Medullary carcinoma of the colon
Metastasis

How to Report an FNA

Specimen Adequacy

1.

Adequate/satisfactory
2.

Inadequate/unsatisfactory
3.

Suboptimal/limited

An Example of a Formal Report of an FNA of the Thyroid

Thyroid, right, FNA
Positive for malignant cells
Papillary thyroid carcinoma
Adequately cellular specimen

Comment: Tall cell variant of papillary carcinoma of the thyroid is suspected.

Cytological Criteria of Common Neoplasms

1.
Papillary Carcinoma of Thyroid
Major Criteria (Fig. 1.33)

Nuclear enlargement

Nuclear overlapping

Nuclear clearing

Nuclear grooving

Intranuclear inclusion

Fig. 1.33

Classic nuclear changes in a papillary carcinoma of the thyroid on Pap stain

Minor Criteria

Squamoid cytoplasm

Cytoplasmic vacuoles

Psammoma body

Thick colloid

Multinucleated giant cells

2.
Medullary Carcinoma of the Thyroid
Major Criteria (Fig. 1.34)

Two populations of cells, epithelioid and spindle cells

Salt-pepper chromatin

Small to inconspicuous nucleoli

Plasmacytoid features

Fig. 1.34

Classic cytological features for a medullary carcinoma of the thyroid on DQ

Minor Criteria

Intranuclear inclusion

Granular and dense cytoplasm

Amyloid

Hyaline globules
3.
Adenoid Cystic Carcinoma of Salivary Gland
Major Criteria (Fig. 1.35)

Small uniform, basaloid cells with high nuclear-to-cytoplasmic ratio, bland nuclei, but hyperchromatic chromatin

Hyaline globules

Fig. 1.35

Diagnostic hyalinizing globules in an adenoid cystic carcinoma on DQ

Minor Criteria

Usually absence of myoepithelial cells

Few stromal fragments

Exclude other entities
4.
Benign Mixed Tumor of the Salivary Gland
Major Criteria (Fig. 1.36)

Epithelial cells

Stromal cells

Metachromatic stroma

Spindle stromal cells

Plasmacytoid myoepithelial cells

Fig. 1.36

Showing an example of benign mixed tumor on DQ

Minor Criteria

Epithelial cell dominant

Stromal cell dominant

Stromal acellular component dominant

Myoepithelial cell dominant

Extensive squamous metaplasia
5.
ADC of the Pancreas
Major Criteria (Fig. 1.37)

Variation in nuclear size in the same group (1:4)

Nuclear enlargement (>2 red blood cells [RBCs])

Nuclear overlapping/three dimensionality

Nuclear membranous irregularity

Fig. 1.37

Showing an example of well-diff ADC of the pancreas on Pap stain

Minor Criteria

Single atypical cells

Tumor necrosis

Prominent nucleoli

Mitosis

Chromatin clearing

Giant tumor cells

Hyperchromatic nuclei
6.
NET of the Pancreas
Major Criteria (Fig. 1.38)

A mixture of small cohesive groups and single cells

Round nuclei with salt-pepper nuclear chromatin

Small nucleoli

Plasmacytoid features

Binucleation

Fig. 1.38

Showing an example of pancreatic NET

Minor Criteria

Occasional large atypical cells

Crushed artifact

Focal necrosis

Multinucleated giant cells

Granular cytoplasm

Striped nuclei
7.
HCC
Major Criteria (Fig. 1.39)

Trabecular fragment >3 cells thick and wrapped by endothelial cells or pseudoglandular formation with production of bile

Special stain for reticulin and an immunostain for cluster of differentiation (CD)34 performed on the cell block section or core biopsy are useful

Fig. 1.39

Showing an example of HCC producing bile on Pap stain

Minor Criteria

Hypercellularity

Many single cells

Naked nuclei

High nuclear-to-cytoplasmic ratio

Few ductal cells
8.
Ductal Carcinoma of the Breast
Major Criteria (Fig. 1.40)

Hypercellularity

Nuclear enlargement (>2.5 RBCs)

Disordered, loosely cohesive epithelial group

Single atypical cells

Nuclear chromatin changes

Fig. 1.40

Showing an example of breast ductal carcinoma on Pap stain

Minor Criteria

Marked nuclear atypia

Tumor necrosis

Mitosis

Prominent nucleoli

Intracytoplasmic lumens

Foamy cytoplasm
9.
Small-Cell Carcinoma of the Lung
Major Criteria (Figs. 1.41 and 1.42 )

Pleomorphic nuclei with salt-and-pepper nuclear chromatin

Very high nuclear-to-cytoplasmic ratio

Single cell necrosis and mitosis

Inconspicuous nucleoli

Fig. 1.41

Showing an example of small-cell carcinoma of the lung on DQ

Fig. 1.42

Showing nuclear molding in a small-cell carcinoma on DQ

Minor Criteria

Crushed artifact

Hypercellularity

Many single cells

Blue body

Nuclear molding

Extensive necrosis

Marked atypical cells
10.
ADC of the Lung
Major Criteria

Three dimensional groups

Glandular, tubular, acinar, or papillary formation

Nuclear enlargement

Chromatin clearing and clumping

Irregular nuclear membrane

Prominent nucleoli

Mucinous material in the background

Minor Criteria

Single atypical cells with plasmacytoid features

Mitosis

Vacuoles in cytoplasm
11.
SCC of the Lung
Major Criteria (Fig. 1.43 )

Two or three dimensional groups

Keratinization

Single atypical cells with dense cytoplasm

Nuclear enlargement

Small nucleoli

Irregular nuclear membrane

No glandular, tubular, acinar, or papillary formation

Mucinous material in the background

Fig. 1.43

Showing an example of well-differentiated SCC of the lung on Pap stain

Minor Criteria

Tumor necrosis

Mitosis

Marked pleomorphic cells

Bizarre cell sharps
12.
Melanoma
Major Criteria (Fig. 1.44)

Large epithelioid cells

Abundant cytoplasm

Large nuclei

Prominent nucleoli

Binucleation

Intranuclear inclusion

Fig. 1.44

Showing an example of melanoma with clear cytoplasm on Pap stain

Minor Criteria

Two populations of cells – epithelioid and spindle

Plasmacytoid appearance

Marked pleomorphic cells

Pigments
13.
Clear Cell RCC
Major Criteria (Fig. 1.45)

Clusters of tumor cells with vascular-rich network

Low nuclear-to-cytoplasmic ratio

Clear or granular cytoplasm

Small to prominent nucleoli

Intranuclear inclusion

Fig. 1.45

Showing an example of clear cell RCC on Pap stain

Minor Criteria

Naked nuclei

Mixed neutrophils, RBCs, and pigment-laden histiocytes with tumor cells
14.
Non–Hodgkin’s Lymphomas
Major Criteria (Fig. 1.46)

Uniform population of lymphoid cells

Classified into small, medium, and large cell size using histiocytes as a reference

Lymphoglandular body

Fig. 1.46

Showing an example of lymphoblastic lymphoma on DQ

Minor Criteria

Cleaved or noncleaved nuclei

Fine granular chromatin

Many mitoses

Single cell or extensive necrosis

Prominent nucleoli

Cytoplasmic vacuoles
15.
Hodgkin’s Lymphoma
Major Criteria (Fig. 1.47)

Reed-Sternberg cells

Hodgkin’s cells

Mixed population of small lymphoid cells, histiocytes, plasma cells, and eosinophils in the background

Fig. 1.47

Showing an example of Hodgkin lymphoma with Reed-Sternberg cells on DQ

Minor Criteria

Granulomas

Fibrosis

Necrosis

Diagnosis of lymphomas should not solely rely on cytological features; instead, it should include (1) cytomorphology, (2) immunohistochemistry (IHC), (3) flow cytometry, and (4) FISH/molecular diagnosis.

Ancillary Studies

IHC

In this section, the focus will be on the application of IHC to undifferentiated neoplasms if a cell block or a small tissue biopsy sample is available, especially carcinoma of unknown origin. The utilities of IHC on other specific entities on each organ will be delineated in each organ-based chapter.

How to Approach Undifferentiated Neoplasms /Tumors of Uncertain Origin

Review hematoxylin- and eosin (H&E)-stained slides .

Morphologic features are fundamental. The very first step is to determine if the lesion is malignant. If a benign/reactive condition is included in the differential diagnosis, caution should be taken when applying any immunostains, since IHC may or may not contribute to this process or may lead one to come to the wrong conclusion. If the lesion is malignant, it is important to review the slides and generate a broad differential diagnosis based on the morphologic features alone. One can be misled by incomplete or inaccurate clinical information .
Consider the basic clinical information such as age, sex, tumor location, and prior malignancy.

After formulating the initial differential diagnostic categories, it is time to consider the patient’s age, sex, tumor location, and any prior malignancy. One should follow the statistics and focus on the common entities in that particular age group of patients and tumor location. Jumping to a conclusion of an uncommon entity in the initial diagnostic workup is not a wise choice .
Re-evaluate morphologic features of the tumor and predict the most likely category, such as carcinoma, melanoma , sarcoma , lymphoma , or germ cell tumor .

Based on the patient’s age, sex, tumor location, prior malignancy, and morphologic features, one should narrow down the initial differential diagnosis to one to three options, if possible. For example: Is this a carcinoma? Is this an ADC? If it is an ADC, what is the likely primary site? Based on the tumor morphology, patient’s age, and tumor location, the literature demonstrated that pathologists were able to correctly identify the tumor origin as their first choice in 50–55% of cases or as their first, second, or third choice in 67–74% of cases .
Determine the first diagnostic IHC panel to order .

There are two likely scenarios. In the first, there is a clear lineage differentiation, such as an ADC/carcinoma. The next question will be: What is the likely primary site? A broad-spectrum cytokeratin cocktail (AE1/3 and CAM5.2 ), cytokeratin (CK)7, CK20 , plus relatively organ-specific markers are recommended .

Determination of a Broad Category of Neoplasm

A cocktail of AE1/AE3 and CAM 5.2 is an effective panel of markers for identifying an epithelial lineage. AE1/AE3 by itself is insufficient to exclude an epithelial lineage. Other broad-spectrum cytokeratins containing keratin 8 and keratin 18, such as clones KL1, OSCAR, MAK6, and 5D3/LP3, are also excellent choices as a screening cytokeratin.

Leukocyte common antigen (LCA) itself is insufficient to exclude a potential diagnosis of hematopoietic neoplasm. Some diffuse large B-cell lymphomas, plasmablastic lymphomas, and anaplastic lymphomas can be negative for LCA. A combination of LCA and CD43 will cover a broad spectrum of lymphomas/myeloid sarcomas .

Vimentin is a non-specific marker; however, a vimentin-negative tumor is unlikely to be a sarcoma (with the exception of alveolar soft part sarcoma), lymphoma, or melanoma . Some carcinomas frequently co-express vimentin. A combination of S100 and sex-determining region Y-box (SOX)10 will detect nearly 100% of melanomas and greater than 80% of spindle cell /desmoplastic melanomas.

Sal-like protein 4 (SALL4 ) and lin-28 homolog A (LIN28) are highly sensitive and specific markers for identifying a tumor of germ cell origin. The markers for determination of a broad category of neoplasms are summarized in Table 1.2.

Table 1.2

Markers for determination of a broad category of neoplasms

Marker/Tumor	Carcinoma	Sarcoma	Melanoma	Lymphoma	GCT	Mesothelioma
CK	+	−	−	−	+/−	+
Vimentin	−/+	+	+	+	−	+/−
S100 /SOX10	−/+	−	+	−	−	−
LCA/CD43	−	−	−	+	−	−
SALL4 /LIN28	−	−	−	−	+	−

Note: GCT giant cell tumor, CK a broad spectrum cytokeratin, SOX10 sex-determining region Y-box 10, LCA leukocyte common antigen, CD43 cluster of differentiation 43, SALL4 sal-like protein 4, LIN28 lin-28 homolog A, “+” >75% of cases are positive, “−” <5% of cases are positive, “+/−” 50–75% of cases are positive, “−/+” <50% of cases are positive

Tissue-Specific Markers

No single antibody is absolutely sensitive and specific for a particular tumor; however, some are especially useful when used in a small panel. Frequently used tissue-specific biomarkers are summarized in Table 1.3.

Table 1.3

Useful markers for identifying tumor origin

Primary site	Markers
Lung ADC	TTF1, napsin A
Breast carcinoma	GATA3 , ER , GCDFP-15, TFF1, MGB
Urothelial carcinoma	GATA3 , UPII/UPIII, S100P, CK5/6 , CK903, p63 , CK20
Squamous cell carcinoma	p40 , CK5/6 , p63 , SOX2, desmocollin-3
RCC , clear cell type	PAX8 /PAX2, RCCma, pVHL , CD10 , KIM-1
Papillary RCC	P504S , RCCma, pVHL , CD10 , PAX8 , KIM-1
Translocational RCC	TFE3
HCC	Arg-1, glypican-3 , HepPar-1, AFP
Adrenal cortical neoplasm	Mart-1 , inhibin-alpha, calretinin, SF-1
Melanoma	S100 , Mart-1 , HMB45 , MiTF, SOX10 , PNL2
Merkel cell carcinoma	CK20 (perinuclear dot staining), MCPyV
Mesothelial origin	Calretinin , WT1, D2-40 , CK5/6 , mesothelin
Neuroendocrine origin	Chromogranin , synaptophysin, CD56,
Upper GI tract	CDH17, CDX2 , CK20
Lower GI tract	CDH17, SATB2 , CDX2 , CK20
Intrahepatic cholangiocarcinoma	pVHL , CAIX, albumin by RNA in situ hybridization
Pancreas, acinar cell carcinoma	Glypican-3 , Bcl-10, antitrypsin
Pancreas, ductal ADC	MUC5AC, CK17, maspin, S100P, IMP3
Pancreas, NET	PR, PAX8 , PDX1, islet-1
Pancreas, solid pseudopapillary tumor	Nuclear beta-catenin, loss of E-cadherin, PR, CD10 , vimentin
Prostate, ADC	NKX3.1 , PSA , PSAP , ERG
Ovarian serous carcinoma	PAX8 , ER , WT1
Ovarian clear cell carcinoma	pVHL , HNF-1B, KIM-1, PAX8
Endometrial stromal sarcoma	CD10 , ER
Endometrial ADC	PAX8 /PAX2, ER , vimentin
Endocervical ADC	PAX8 , p16, CEA , HPV in situ hybridization, loss of PAX2
Thyroid follicular cell origin	TTF1, PAX8 , thyroglobulin
Thyroid medullary carcinoma	Calcitonin, TTF1, CEA , chromogranin
Parathyroid neoplasm	PTH, GATA3 , chromogranin
Hyalinizing trabecular adenoma of the thyroid	MIB-1 (unique membranous staining pattern)
Salivary duct carcinoma	AR, GCDFP-15, HER2, GATA3
Mammary analogue secretory carcinoma of the salivary gland	S100 , GATA3 , MGB, GCDFP15
Thymic origin	PAX8 , p63 , CD5
Seminoma	SALL4 , OCT4 , CD117 , D2-40
Yolk sac tumor	SALL4 , glypican-3 , AFP, GATA3
Embryonal carcinoma	SALL4 , LIN28, OCT4 , NANOG, CD30 , SOX2
Choriocarcinoma	Beta-HCG, CD10 , GATA3
Sex cord-stromal tumors	SF-1, inhibin-alpha, calretinin, FOXL2
Vascular tumor	ERG, CD31, CD34, Fli-1
Synovial sarcoma	TLE1, cytokeratin
Chordoma	Cytokeratin, S100
Desmoplastic small round cell tumor	Cytokeratin, CD99 , desmin , WT1 (N-terminus)
Alveolar soft part sarcoma	TFE3
Rhabdomyosarcoma	Myogenin , desmin , MyoD1
Smooth muscle tumor	SMA , MSA, desmin, calponin
Ewing sarcoma /PNET	NKX2.2 , CD99 , Fli-1
Myxoid and round cell liposarcoma	NY-ESO-1
Low-grade fibromyxoid sarcoma	MUC4
Epithelioid sarcoma	CD34, loss of INI1
Atypical lipomatous tumor	MDM2 (MDM2 by FISH is a more sensitive and specific test), CDK4
Histiocytosis X	CD1a, S100
Angiomyolipoma	HMB45 , SMA, PNL2
Gastrointestinal stromal tumor	CD117 , DOG1
Solitary fibrous tumor	STAT6 , CD34, Bcl2, CD99
Myoepithelial carcinoma	Cytokeratin and myoepithelial markers. May lose INI1
Myeloid sarcoma	CD43, CD34, MPO
Follicular dendritic cell tumor	CD21, CD35
Mast cell tumor	CD117 , tryptase

Note: ADC adenocarcinoma, TTF1 thyroid transcription factor 1, GATA3 GATA binding protein 3, ER estrogen receptor, GCDFP-15 gross cystic disease fluid protein 15, TFF1 trefoil factor 1, MGB mammaglobin, UP uroplakin, S100P placental S100 , CK cytokeratin, SOX sex-determining region Y-box, RCC renal cell carcinoma, PAX paired box gene, RCCma renal cell carcinoma marker, pVHL von Hippel-Lindau tumor suppressor, CD cluster of differentiation, KIM-1 kidney injury molecule 1, P504S alpha-methylacyl-CoA racemase, TFE3 transcription factor E3, HCC hepatocellular carcinoma, Arg-1 arginase-1, HepPar-1 hepatocyte paraffin-1, AFP alpha-fetoprotein, Mart-1 melanoma-associated antigen recognized by T cells 1, SF-1 steroidogenic factor 1, HMB45 human melanoma black 45, MiTF microphthalmia-associated transcription factor, PNL2 melanoma-associated antigen PNL2, MCPyV Merkel cell polyomavirus, WT1 Wilms’ Tumor 1, D2-40 podoplanin, GI gastrointestinal, CDH17 cadherin-17, CDX2 caudal-type homeobox 2, SATB2 special AT-rich sequence-binding protein 2, CAIX carbonic anhydrase IX, MUC mucin, maspin mammary serine protease inhibitor, IMP3 IMP3 insulin-like growth factor II messenger RNA-binding protein 3, NET neuroendocrine tumor, PR progesterone receptor, PDX1 pancreatic duodenal homeobox 1, PSA prostate-specific antigen, PSAP prostate-specific acid phosphatase, ERG ETS-related gene, NKX3.1 NK3 homeobox 1, HNF-1B hepatocyte nuclear factor 1 beta, CEA carcinoembryonic antigen, HPV human papilloma virus, MIB-1 mindbomb homolog 1, AR androgen receptor, SALL4 sal-like protein 4, LIN28 lin-28 homolog A, OCT4 octamer-binding transcription factor 4, NANOG NANOG homeobox, Beta-HCG Beta human chorionic gonadotropin, FOXL2 forkhead box L2, Fli-1 friend leukemia virus integration-1, TLE1 transducin-like enhancer of split 1, MyoD1 myogenic differentiation 1, SMA smooth muscle actin, MSA muscle-specific actin; PNET primitive neuroectodermal tumor, NKX2.2 NK2 homeobox 2, NY-ESO-1 cancer/testis antigen 1B; INI1 integrase interactor 1, MDM2 mouse double minute 2 homolog, FISH fluorescence in site hybridization, CDK4 cyclin-dependent kinase 4, DOG1 discovered on GIST-1, Bcl2 B-cell CLL/lymphoma 2, MPO myeloperoxidase

Co-expression of Cytokeratin and Vimentin

Follicular, papillary, and medullary thyroid carcinomas are nearly 100% positive for vimentin. Metaplastic breast carcinoma usually expresses both cytokeratin and vimentin in addition to high molecular weight cytokeratins and myoepithelial markers. Alveolar soft part sarcoma is a rare sarcoma which has no immunoreactivity for vimentin. Tumors that express both cytokeratin and vimentin are described in Table 1.4.

Table 1.4

Tumors that frequently or rarely co-express cytokeratin and vimentin

Carcinomas that frequently express both	Mesenchymal tumors that frequently express both	Carcinomas that rarely express both
RCC	Synovial sarcoma	Breast carcinoma
Anaplastic thyroid carcinoma	DPSRCT	Ovarian carcinoma
Endometrial carcinoma	Epithelioid sarcoma	GI carcinoma
Thyroid carcinomas	Epithelioid angiosarcoma	Small-cell carcinoma
Sarcomatoid carcinoma	Malignant rhabdoid tumor	Lung non-small-cell carcinoma
Mesothelioma	Leiomyosarcoma	Prostatic carcinoma
Myoepithelial carcinoma	Chordoma
Metaplastic breast carcinoma	Adamantinoma

Note: RCC renal cell carcinoma, DPSRCT desmoplastic small round cell tumor, GI gastrointestinal

Expression of Epithelial Markers in Non-epithelial Neoplasms

Expression of cytokeratin is not restricted to epithelial neoplasms. Keratin is commonly expressed in some tumors with evidence of epithelial differentiation, such as synovial sarcomas, epithelioid sarcomas, desmoplastic small round cell tumors, chordomas, adamantinoma, and myoepithelial carcinomas. Other mesenchymal tumors can also express cytokeratin, although with a low frequency, including angiosarcomas, epithelioid hemangioendotheliomas, epithelioid leiomyosarcomas, and meningiomas. Aberrant expression of cytokeratin, which tends to be focal, has been reported in other tumors, including undifferentiated pleomorphic sarcomas, rhabdomyosarcomas, malignant rhabdoid tumors, and peripheral nerve sheath tumors, clear cell sarcomas, plasmacytomas, diffuse large B-cell lymphomas, anaplastic large-cell lymphomas, and melanomas .

Expression of Hematopoietic Markers in Non-hematopoietic Neoplasms

CD5 has been reported in thymic carcinoma, breast carcinoma, colonic ADC, pancreatic ADC, and lung ADC. CD138 is also frequently positive in SCC and can be positive in breast carcinoma, ovarian carcinoma, adrenal cortical carcinoma, and RCC .

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Tags: Handbook of Practical Fine Needle Aspiration and Small Tissue Biopsies

Jan 30, 2018 | Posted by admin in PATHOLOGY & LABORATORY MEDICINE | Comments Off

Basicmedical Key

Fastest Basicmedical Insight Engine