IHC- interpretare.ppt

7/22/2019 IHC- interpretare.ppt

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Markeri IHC in diagnosticul

tumorilor epiteliale si

conjunctive


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BCL-2

Reacts with the BCL2 oncoprotein encoded by a gene involved in the t(14;18) chromosomal

translocation;

Bcl-2 ("B-cell lymphoma/leukaemia-2"), which acts as an inhibitor of apoptosis, was originally

discovered as a proto-oncogene in low-grade B-cell lymphomas.

In the adult organism Bcl-2 expression is generally confined to cells that are rapidly dividing and

differentiating. In lymphocytes, Bcl-2 is highly expressed in T-cells, pro-B cells and mature B-cells (wherelifespan is extended) while downregulated in germinal center B-cells (where apoptosis forms part of the

developmental pathway in order to select only cells producing antibodies with high avidity)

Overexpression of Bcl-2 is common in many types of cancer, including non-Hodgkin's lymphoma

and leukaemias, adenocarcinomas (e.g., prostate, colorectum, stomach, and lung), squamous cell

carcinoma, small cell carcinoma, neuroblastoma and various sarcomas. Among the latter, strong Bcl-2

positivity has particularly been demonstrated in gastrointestinal stromal tumor, solitary fibrous tumor, and

synovial sarcoma, while fibromatosis and "malignant fibrous histiocytoma" are usually negative.

Among malignant lymphomas, Bcl-2 protein overexpression is often caused by chromosomal translocation

(14;18) with Bcl-2 gene rearrangement. This is especially seen in follicular lymphoma. bcl-2 is expressed in

almost 100% of the grade I lymphomas, in >80% of the grade II and in 75% of the grade III lymphomas.

Follicular lymphoma of the skin is often bcl-2 negative


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Bcl-2 in ggl limfaticBcl-2 in SLL

Bcl-2 in GIST


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BCL-6:

encodes a 706 amino acid nuclear protein (repressor

of p53), is rearranged in about 30% of diffuse large B-

cell lymphomas, and is expressed predominantly innormal germinal center B cells and related

lymphomas;

The antibody gives a strong nuclear labeling of BCL6

protein in follicular lymphomas, diffuse large B-celllymphomas, Burkitt's lymphomas, and nodular,

lymphocyte-predominance Hodgkin's disease.


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Bcl-6 in ggl limf Bcl-6 in limfom folicular


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ALCLALK in ALCL


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CD5-

The CD5 antigen is a 67 kDa transmembrane glycoprotein expressed on the surface of practically allmature human T-cells (about 10% of CD4+ T-cells being CD5 negative). In immature (CD34+) T-cells, CD5 is weakly expressed, the intensity of expression increasing with maturation.

CD5 is also expressed in a small subset of normal human B-cells (20% of B-cells in the peripheralblood, scattered cells in the lymph node mantle zone). The CD5+ cells are probably involved in B-Tinteraction and their ligand is CD72 which is expressed on all B cells.

It appears that CD5+ B-cells on activation primarily produce IgM. They also produce moreautoantibodies than normal CD5 negative B-cells. Thus, the CD5+ B-cell population is expanded inrheumatoid arthritis and systemic lupus erythematosus.

Neoplasms

CD5 is detected in most T-cell lymphomas and leukaemias, including 75% of peripheral T-celllymphomas and 85% of T-ALL cases. Lack of CD5 in the latter signifies a worse prognosis.

Among B-cell lymphomas, more explicit CD20+ small-cell lymphomas, small lymphocytic lymphoma

and mantle cell lymphoma are CD5+, whereas follicular lymphoma, marginal zone lymphoma andlymphoplasmacytoid lymphoma are CD5 negative. CD5 is detected in 5% of acute myeloidleukaemias.

CD5 has been detected in some cases of thymic carcinoma and atypical thymoma. Othercarcinomas are CD5 negative.


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CD10 CD10 is a single-chain cell surface glycoprotein, 90-110 kDa, also designated

common acute lymhoblastic leukaemia antigen (CALLA)

CD10 is present on the cell surface of bone marrow stem cells andmyelopoietic cells (including neutrophils), follicular centre cells, few mature B-lymphocytes;

CD10 is also found in enterocytes in the upper part of the intestinal tract(brush border,in liver (bile canaliculi), kidney (glomerular and proximal tubularcells), pulmonary alveolar cells, myoepithelial cells of breast.

CD10 is expressed in most cases of precursor B lymphoblasticleukaemia/lymphoma, follicular lymphoma, and Burkitt lymphoma. CD10 isfound in some cases of diffuse large B-cell lymphoma, and mantle celllymphoma;

small lymphocytic lymphoma, marginal zone lymphoma, andlymphoplasmacytoid lymphomaare negative.

CD10 is found in almost all cases of endometrial stromal sarcoma, in mostcases of hepatocellular carcinoma (distinct canalicular pattern), renal cellcarcinoma (clear cell and papillary types, but not chromophobic type)


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Limfom folicular Carcinom renal


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CD15 a haematopoietic differentiation antigen expressed on

most terminally differentiated myeloid cells includinggranulocytes, eosinophils, mast cells,

monocytes/macrophages, and Langerhans' cells. The positivity for CD15 is characteristic of Hodgkins

cells in classical Hodgkins disease (HD);

It is expressed in great majority of nodular sclerosis(NS), mixed cellularity (MC), lymphocyte depletion(LD) and lymphocyte rich-classical HD cases, but not inmalignant cells of lymphocyte predominance (LP) HD(L&H cells, popcorn cells)


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CD20 normal CD20 in CLL


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CD23- low affinity IgE receptor, Leu-20, FceRII;

- In humans, main cellular expression of CD23 is found in B-lymphocytes(strong expression in activated germinal center B-cells, weaker stainingof resting mantle zone B-cells), monocytes, follicular dendritic cells(FDCs) predominately in the apical light zone of the germinal center;

- CD23 is typically expressed in chronic lymphocytic leukemia (CLL) - thestrongest expression is characteristically present in proliferationcenters.

- sometimes in follicular lymphoma,

- rarely in marginal zone and lymphoplasmacytic lymphoma,

- not in mantle cell lymphoma.- !! CD23 is also frequently used to demonstrate benign follicular

dendritic cells in the background of follicular lymphoma


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CD30 CD30 is a member of the tumor necrosis factor receptor (TNF-R)

superfamily;

CD30 is found in activated B lymphocytes, plasma cells, Tlymphocytes, NK cells, monocytes;

CD30 is expressed in classical Hodgkins disease (cHD),anaplastic large cell lymphoma (ALCL), anaplastic variant ofdiffuse large B-cell lymphoma (av-DLBCL), and CD30 positivecutaneous lymphoproliferative disorder.

Some cases of mycosis fungoides can have significant CD30

expression; Expression of CD30 has also been demonstrated in embryonal

carcinoma and some seminomas.


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CD30 in normal activated B cells CD 30 in HD

CD30 in carcinom embrionar


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CD45 CD45 is a family of single chain transmembrane glycoproteins;

CD45 is expressed on cells of the human haematopoietic lineage with theexception of mature red cells.

CD45 is lost in megakaryocytes and plasma cells.

It is not detected on differentiated cells of other tissues.

CD45 has intrinsic tyrosine phosphatase activity and is essential fordevelopment and effector functions, playing an important role in signaltransduction, inhibition or upregulation of various immunological functions.

CD45 is detected in the large majority of haematolymphoid neoplasms, i.e.,leukaemias and malignant lymphomas.

Overall, about 90% of malignant lymphomas are CD45 positive. The

proportion is lower among precursor B-cell neoplasms (80% of B-ALL) andlarge cell anaplastic lymphomas, and only about 10% of plasmacyticneoplasms are positive.

In Hodgkin lymphoma, the L&H cells in the LP-type are always positive, whileReed-Sternberg cells in classic Hodgkin lymphoma are negative or only show afaint cytoplasmic staining.


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CD68: antibodies detect a glycoprotein with a molecular

weight of approximately 110 kD, localized in thecytoplasm, often with relation to lysosomes.

Positive staining is seen in different types ofmacrophages of monocyte lineage and antibodies alsoreacts with myeloid precursor cells in the bonemarrow.

Expressed in fibrous-histiocytic tumours and

Langerhans cell histiocytosis, subtypes of myeloidleukaemia (depending on the Ab used), someepithelial neoplasms, epithelioid cells of somemalignant melanomas


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CD68 in celule Kupffer


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CD31

transmembrane glycoprotein, 130-140 kDa, alsodesignated platelet-endothelium cell adhesion molecule(PECAM-1), belonging to the immunoglobulin super family.

CD31 is strongly expressed in endothelial cells and weaklyexpressed in megakaryocytes, platelets, occasional plasmacells, lymphocytes (especially marginal zone B-cells,peripheral T-cells) and neutrophils.

CD31 is expressed in the vast majority of all types ofvascular neoplasms, such as hemangioendothelioma,angiofibroma, hemangioma, and angiosarcoma.

CD 31 is also expressed in most cases of Kaposi sarcoma


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CD31 in hemangioendoteliom infiltrativ in

intestin


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In carcinomas p63 is a very useful marker for squamous, urothelial andmyoepithelial differentiation. The same tumours are usually expressingcytokeratin 5. However, p63 often shows a more extended reaction.

An important criterion for the diagnosis of prostate adenocarcinoma is theabsence of basal cells. As these can be difficult to identify in routinesections, immunohistochemical identification of p63 and cytokeratin 5

may increase the sensitivity and specificity. Since negative staining for highmolecular weight cytokeratin(HMW-CK) in atypical prostate glands maynot be sufficient for a definitive diagnosis of malignancy, p63 may enhancethe ability to diagnose limited prostate cancer. However, p63 should beused in conjunction with HMW-CK and AMACR. A cocktail staining isapplicable. The combination of p63 and HMW-CK increases the sensitivityof basal cell detection

P63 is used in identifying invasive foci in breast carcinomas which lack themyoepithelial cell layer.
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P63 in prostata normala


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CEA A glycoprotein comp of Ig superfamily (adhesion molecule);

In normal adult tissue, CEA is expressed in the apical border and, to alesser extent in the cytoplasm, of the columnar cells of colon, smallintestine, and stomach (surface epithelium, mucous neck cells andweakly in pyloric mucous cells), pancreatic ducts, secretory epitheliaof sweat glands, squamous epithelial cells of the tongue, esophagusand uterine cervix, and urothelium. The prostate is negative (apartfrom urothelium lined secretory ducts).

CEA is expressed in epithelial cell membranes and in the cytoplasm ofthe cells in almost all cases of colorectal adenocarcinoma as well as ahigh proportion of adenocarcinomas of the salivary glands, esophagus,

stomach, biliary tract, pancreas, small intestine, lung, uterine cervixand ovary (mucinous type).


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Cadherins Cadherins are a family of calcium-dependent transmembrane

cell adhesion glycoproteins. In connecting cells they comprise apart of the zonula adherens and desmosomes.

The following tumours are almost always positive:

adenocarcinoma of colorectum, stomach, pancreas, prostate,endometrium, uterine cervix, and thyroid.

Among ovarian carcinomas, the mucinous type is almost alwayspositive, while varying positivity is seen in the other types.

Among breast carcinomas the ductal type (including thetubulolobular subtype) is almost always positive (at least in partof the tumour) while the lobular type is negative in 8590 %.


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EMA in mezoteliom


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Calretinin 32 kDa member of the superfamily of calcium-binding proteins.

It is abundantly expressed in central and peripheral neural tissues,particularly in the retina and in the neurons of the sensory pathways

it is also expressed in steroid producing cells (adrenal cortical cells,testicular Leydig cells, ovarian theca interna cells), testicular Sertolicells, rete testis, ovarian surface epithelium, some neuroendocrinecells, breast glands, eccrine sweat glands, hair follicular cells, thymicepithelial cells, endometrial stromal cells, and fat cells

Calretinin is also expressed by both normal and neoplastic mesothelialcells;

it is an useful marker for the identification of malignant mesotheliomas ofthe epithelial type and for the differentiation of these malignancies of lungadenocarcinoma

In calretinin positive cells, the protein is generally found in both thecytoplasm and nuclei.


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Mezoteliom


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Actina- clona HHF35 Labels myocardial, skeletal and smooth muscle cells as

well as myoepithelial cells. The antibody recognizesrhabdomyosarcomas, leiomyomas and

leiomyosarcomas, and also reacts with'myofibroblasts' in the stroma of certain tumorsincluding many carcinomas

Actina - clona 1A4

This antibody labels smooth muscle cells,

myofibroblasts and myoepithelial cells, and is usefulfor the identification of leiomyomas, leiomyosarcomasand pleomorphic adenomas


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Actina- LMS


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Caldesmon in leiomiom


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Desmin Desmin is an intermediate filamentprotein (53

kDa) expressed in all striated muscle cells andmost smooth muscle cells; Desmin play no role incontractility but serves to maintain the orientationof actin and myosin filaments and may also play arole in nuclear transcription

Desmin is detected in most tumours of myogenicorigin, e.g., leiomyosarcoma andrhabdomyosarcoma
http://www.nordiqc.org/Epitopes/Cytokeratins/Intermediate_filaments.htmhttp://www.nordiqc.org/Epitopes/Cytokeratins/Intermediate_filaments.htm


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Vimentina Vimentin (57 kDa) is the most ubiquituos intermediate filamentprotein and the first to be expressed during cell

differentiation. All primitive cell types express vimentin but in most non-mesenchymal cells it is replaced by otherintermediate filament proteins during differentiation.

Vimentin is expressed in a wide variety of mesenchymal cell types fibroblasts, endothelial cells etc., and in anumber of other cell types derived from mesoderm, e.g., mesothelium and ovarian granulosa cells.

However, in non-vascular smooth muscle cells, vimentin is often replaced by desmin. In striated muscle, vimetin isalso replaced by desmin. However, during regeneration, vimentin is reexpressed.

Cells of the lymfo-haemopoietic system (lymphocytes, macrophages etc.) also express vimentin, sometimes in

scarce amounts. Vimentin is also found in mesoderm derived epithelia, e.g. kidney (Bowman capsule), endometrium and ovary

(surface epithelium), in myoepithelial cells (breast, salivary and sweat glands), an in thyroid gland epithelium

Vimentin is present in many different neoplasms but is particulary expressed in those originated frommesenchymal cells. Sarcomas e.g., fibrosarcoma, malignt fibrous histiocytoma, angiosarcoma, and leio- andrhabdomyosarcoma, as well as lymphomas, malignant melanoma and schwannoma, are virtually always vimentinpositive .

Mesoderm derived carcinomas like renal cell carcinoma, adrenal cortical carcinoma and adenocarcinomas from

endometrium and ovary usually express vimentin. Also thyroid carcinomas are vimentin positive.

Any low differentiated or sarcomatoid carcinoma may express some vimentin.
http://www.nordiqc.org/Epitopes/Cytokeratins/Intermediate_filaments.htmhttp://www.nordiqc.org/Epitopes/Cytokeratins/Intermediate_filaments.htm


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Myo D1 The MyoD1 protein is a 45 kDa nuclear phosphoprotein

which induces myogenesis through transcriptionalactivation of muscle-specific genes;

Nuclear expression of MyoD1 is restricted to skeletalmuscle tissue and has been demonstrated to be a sensitivemarker of myogenic differentiation;

The antibody strongly labels the nuclei of myoblasts indeveloping skeletal muscle tissue, whereas the majority ofadult skeletal muscle is negative;

MyoD1 immunostaining has been demonstrated in themajority of rhabdomyosarcomas of various histologicalsubtypes.


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Myogenin

Myogenin belongs to a family of regulatory proteins

essential for muscle development.

Expression of myogenin is restricted to cells of skeletalmuscle origin, and appears to be inversely related to

the degree of cellular differentiation.

The antibody recognizes an epitope located in the

amino acid region 138-158 of the myogenin protein. It labels nuclei in the majority of human

rhabdomyosarcomas and Wilms' tumors


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AFP (alfa feto protein) - a 70 kDa glycoprotein, synthesized by the cells of the

embryonic yolk sac, fetal liver and fetal intestinaltract.

Expression of AFP has been demonstrated in manyhepatocellular carcinomas and in gonadal andextragonadal germ cells tumors, including yolk sactumors.

The antibody may be useful for the identification ofnon-neoplastic and neoplastic liver diseases, yolk sactumors and mixed germ cell tumors


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AFP in tumora sac yolk


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WT-1 The WT1 gene located at chromosome 11p13 codes for a transcription factor, a DNA-binding

nucleoprotein, 52-62 kDa, that plays a role primarily in the development of genitourinaryorgans.

In normal epithelia, nuclear WT1 expression is largely restricted to ovary (surface epitheliumand inclusion cysts) and fallopian tube, while WT1 is not found in endometrial or cervicalepithelium. As regards nonepithelial cells, nuclear WT1 is found in mesothelium and somesubmesothelial stromal cell

Among epithelial tumours, nuclear WT1 is strongly expressed in ovarian serous carcinoma(97% of the tumours, usually a widespread reaction), peritoneal serous carcinoma, ovariantransitional carcinoma, and about half of ovarian endometrioid carcinoma (grade 2 and 3 butnot grade 1). Also metanephric adenoma is positive

Among nonepithelial tumours, nuclear WT1 is strongly expressed in the large majority ofmalignant mesothelioma and sex cord-stromal tumours.

Nuclear WT1 has moreover been demonstrated in Wilms' tumour (about 50% of the cases,involving epithelial, stromal and blastemal elements), malignant rhabdoid tumour,

adenomatoid tumour, endometrial stromal sarcoma, uterine leiomyosarcoma, mixedmullerian tumour, as well as in some malignant lymphomas (lymphoblastic and Burkitt'slymphoma), and most cases of acute leukaemia.


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WT-1 in mezoteliul normal WT-1 in mezoteliom


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Melan A in epiteliul normal Melan A in melanom


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Inhibin is a dimeric glycoprotein hormonecomprised of an and a subunit.

It is produced by ovarian granulosa cells andinhibits the production or secretion of pituitary

gonadotropins, particularly follicle-stimulatinghormone.

The antibody was raised against the terminal 1-32amino acid sequence of the inhibin subunit.

In abnormal ovarian tissues, inhibin is asensitive marker for the majority of sex-cord-stromal tumors.


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TTF-1 in carcinom tiroidian folicular


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The Ki-67 antigen is a large nuclear protein (345,395 kDa) preferentially expressed during all active

phases of the cell cycle (G1, S, G2and M-phases),

but absent in resting cells (G0-phase). In diagnostic histopathology and cell biology,

antibodies against the Ki-67 antigen have proven

valuable by allowing direct monitoring of the

growth fraction of normal and neoplastic cells


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Ki-67 in mucoasa colonica normala


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HMB-45 Vimentina


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Carcinom cu celule Merkel: Aspect monomorf ; celule cu citoplasma putina ;

nuclei rotunzi, vacuolati, nucleolati, cromatina in saresi piper; numerosi nuclei fragmentati, stroma cunumeroase vase cu endoteliu inalt

IHC : poz pentru: citokeratine cu greutate mica (CK 20- aspect punctiform,

perinuclear, rar intalnit in alte organe)

Neurofilamente;

Enolaza neuron specifica Cromogranina, sinaptofizina, VIP

Diagn. Diferential cu carc neuroendocrin cu cel mici de plaman(CK7 poz si TTF poz);


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Plaman si pleura


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Plaman si pleura

Mezoteliom AA pozitiv/ PAS negativ

IHCpoz pt. : calretinin, CK 5/6 si WT1, EMA

neg: CEA, B72.3 si MOC-31 (poz in adenoc)


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TTF in adenoc pulmonar


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TTF in adenoc pulmonar


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Carcinom cu dezvoltare lepidica (fostul carcinom bronhiolo-alveolar) !! Subtipul mucinos este CK 20 poz si TTF-1poz

MUC3 si MUC6 poz ( diagn. diferential cu ADK);

Carcinomul cu cel mica:

- caracteristic: nuclei mulati, hipercromatici, cromatina fina,nucleoli absenti, citoplasma putina, mitoze numeroase ( posibil caaceasta celula apare din celule epiteliale si in cursul tranformarii malignesufera diferentiere endocrina).

IHC: - pozitivitate variabila pentru : neurofilamente, Leu-7, cromogranina,sinaptofizina, enolaza neuron specifica (marker seric de asemenea!),keratine.

CD99 - neg (dgn dif cu PNET/ sarcom Ewing)

TTFpoz in aprox. 85% de cazuri;


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Sinaptofizina


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Sinaptofizina


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Tumora cu celule clare (sugar cell tumor) HMB-45, enolaza, sinaptofizina, focal S-100.

Metastaze!

Tiroida


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Tiroida

Carcinom papilar tiroidian CK 7+/CK 20

CK19 +

HMW CK 34betaE12 +

Tireoglobulina, TTF-1 + (intensitate mai scazuta de

obicei decat in carc folicular);

Alti markeri poz: S100, EMA, CEA, galectin, ER,HBME-1;


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TTF in carc folicular tiroidian


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metastatic


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Tract digestiv


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Gastric carcinoma MUC-1+: tip intestinal;

MUC5AC+: tip difuz; (cardia)

MUC2+ : tip mucinos CEA, EMA, LMW CK + ( dar cateodata CK13, 16);

CK7 + (70% din cazuri);

CK20 + (20%);

Hepatoid ADK: Hep- Par-1+ si AFP +


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CK7

CEA


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Tumori stromale gastrice: Origine: celule Cajal, celule de origine

mezodermica, cu rol in coordonarea activitatatii

contractile a muschiului neted; IHC :

CD117 +

CD34 +

Ki-67

CD117


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CD117


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Tumori cu celule endocrine WDNET (tumora endocrina bine diferentiata su

carcinoid) :

arhitectura microglandulara, trabeculara, mai rarinsulara

Nuclei regulati si normocromatici, rare mitoze, necroza

absenta, vascularizatie bogata.

IHC : - NSE, CRG, SYN, keratine


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Carcinom neuroendocrin bine diferentiat Aceleasi caracteristici microscopice + trasaturi

de atipie: necroza, mitoze (>2%), caracter invaziv

Aceiasi markeri neuroendocriniCarcinom cu celule mici ( carcinom endocrin slab

diferentiat)analog carc cu celule mici pulmonar

- comportament agresiv (Ki-67 >30%),

- de obici cromogranina este absenta sau

prezenta focal, NSE si sinaptofizina intens poz

Intestin subtire


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Tumori endocrine: Origine in celulele endocrine ale glandelor

Lieberkuhn;

Pozitivitate: CEA, CK7(10%), CK20 (20%); Markeri neuroendocrini: Syn, NSE, CRG, PGP9.5,

Leu7;


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Boala celiaca (sprue) Atrofia vilozitatilor, infiltrat inflamator cu limfocite Tc

(CD3 si CD8 pozitive) in corion si intraepitelial;

!sprue refractar se caracterizeaza prin prezenta LTgamma delta

Boala Whipple

- Generata de Tropheryma whipelii;

- Mi: plaje de macrofage in lamina propria ce determinadistorsiuni arhitecturale ale vilozitatilor intestinale si

care contin in citoplasma material PAS pozitiv datoritabacililor;

- IHC : CD4/ CD8 LT scazut;


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GIST

ADK

Limfoame


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Intestin gros Adenocarcinom clasic :

MUC1 si MUC3 poz

CK20 poz/ CK 7 neg CEA poz

CDX2 poz (poz de asemenea in carcinomul mucinos

ovarian si de vezica urinara);

Tag-72 (mAb 72.3) poz (de asemenea si in polipiihiperplazici si adenomatosi si chiar si in mucoasa

normala).


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CDX2

nuclear

marker


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Canal anal Carcinom scuamos

IHC- HPV

Boala Paget: CK7 poz, CK20+/-, GCDFP+/- ( pattern diferitde adenocarcinomul clasic care este CK7-).

Melanom


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Ficat: Carcinom hepatocelular:

Pozitivitate pentru : AFP, keratine: CK8 (CAM 5.2) si CK7 (intr-un nrmic de cazuri), EMA, Hep-Par-1 (mAb ce interactioneaza cu oproteina citoplasmatica inca necunoscuta prezenta in hepatocitenormale si neoplazice).

MOC31negativ (pozitiv in colangiocarcinom si metastazehepatice);

CEAnegativ sau focal pozitiv (ajuta in diagnosticul diferentialpentru ca este pozitiv in carcinomul de cai biliare si in carcinoamemetastatice) ! Pozitivitate de tip canalicular!

Pozitivitate de asemenea la ER si AR.

Tumorile bine diferentiate: laminina, fibonectina

Vasele sunt pozitive la CD34, ceea ce nu se intampla pentrusinusoidele hepatice.


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Colangiocarcinom Coloratie pentru mucina pozitiva (!)

IHC- pozitivitate pentru CEA (pozitivitate

citoplasmatica si luminala !), EMA, Cam 5.2 (LMWCK), AE1/AE3 (HMW CK).

Profilul CK in colangiocarcinomul intrahepatic

(CK7+/CK20+) este diferit fata de

colangiocarcinomul extrahepatic (CK7+/CK20-)


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FVIII related antigen


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Pancreas Adenocarcinom ductal- pozitivitate pentru:

EMA, keratine (CK 7,8, 18, 19, 15, 17, 20, 5/6, 10, 13)

CEA, CA19-9, B72.3 MUC1 (dgn. diferential cu carcinomul papilar

intraductal, carcinomul ampular si cel mucinos)

Glanda suprarenala


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Tumori de corticosuprarenala (adenom/carcinomde corticosuprarenala):

Pozitivitate pentru : vimentina, syn, inhibina si MelanA

Negativitate pentru: cromogranina Pozitivitate de asemenea pentru calretinin (focal), bcl-

2, keratine ( in special adenoamele, focal si sporadic)

!!Adenoamele au expresie mai scazuta pentru

vimentina si mai crescuta pentru LMW CK. Negative pentru :EMA, CEA, B72.3


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Tract genital femininC i


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Cervix

CIN P16- inhibitor de CDK inactivat de HPV-E7, ceea ce

implica ca supraexpresia P16 indica prezenta HPV de

risc inalt- in leziunile CIN II si CIN III mai mult de

jumatate din grosimea epiteliului prezinta pozitivitate(2/3 -1/1);

exista leziuni de grad inalt p16 negative !!!

KI-67in mod normal prezent numai la nivelul

stratului parabazal; in CIN IIindica rata deproliferare inalta; in CIN IIIprezent in toata

grosimea epiteliului.


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Carcinom scuamos invaziv Pozitivitate pentru :

Keratine

P63

CEA

Adenocarcinom endocervical:

-! Coloratii histochimice si marcaje IHC pentru mucina poz (prezdifuz intracelular)

- pozitivitate pentru CEA

- negativitate pentru vimentina

- negativitate sau prez slaba pentru ER, PR

-HPV prezent (col IHC pentru HPV sau p16)Toate acestea ajuta la diagnosticul diferential cu adenoc. endometrioidde endometru! (atentie la carcinomul seros de endometru care estepozitiv la p16)


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(Adeno)carcinom mezonefric:

CD10+

Calretinin +

Carcinom neuroendocrin- NSE +

- Cromog + (cazurile bine diferentiate)

- Syn +

- Serotonin

- CEA

- keratine


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Uter Adenocarcinom endometrioid:

Keratine 7, 8, 18, 19 +

Vimentina + (65-80%)

CEA + in ariile de metaplazie scuamoasa (! Diagn diferential cu

adenoc endocervical)

CA125 +

ER, PR (pozitivitatea cea mai mare in adenoc endometrioid , urmatde carcinomul papilar seros si carcinomul cu celule clare);

! Carc adenoscuamos de grad inalt este neg la ER, PR;

!WT-1 pozitiv in carc papilar seros ovarian si neg in carc papilarseros de endometru si alte carcinoame primare de endometru


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Tumori stromale uterine Mi

Constit din celule mici uniforme, asem celor din stroma endom, invelite defibre de reticulina;

Arhitectura multinodulara

Arteriole spiralate, unele cu pereti hialinizati;

Focare de hialinizare si izolate celule spumoase;

Absenta vaselor mari cu perete gros

Przenta spatiilor de clivare

- IHC:

- CD10 +

- vimentina +

- actin + (de obicei)

- ER, PR +- Desmin, -/ + (uneori prez. focal);

- h-Caldesmon

- S100 -


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Tumori combinate musculare si stromale(stromomioma):

MIaspect caract de starbust a componentei

musculare netede IHC : CD10+

Desmin, h-Caldesmon poztive pe ariile starbust


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Tumori uterine similare tumorilor ovariene cuorigine in cordoanele sexuale:

IHC:

CD99 + Inhibin +


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Tumori mixte mulleriene maligne: Aspect mixt constituit din elemente

carcinomatoase (de tip glandular : endometrioid,

celula clara sau papilar seros) si elemente

sarcoma-like homologe (de tip fibro sau

leiomiosarcom) sau heterologe ( condro sau

osteosarcom);

Pot fi intalnite elemente scuamoase, slabdiferentiate;


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Tumori de muschi neted(leiomiom/leiomiosarcom)

Actina, desmin, calponin, h-caldesmon +

Vimentin+ LMW keratins (CAM 5.2)+ (de obicei)

ER, PR + ( cu intensitate mai mare in leiomioame

decat in leiomiosarcoame);


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Ovar Tumori epiteliale seroase

IHC

CK7+

CK20-

CK , 18, 19, EMA, B72.3 +

S100 + in special in t. borderline

WT-1+ difuz in carcinoamele seroase (la fel in mezotelioameperitoneale, mai putin carcinoamele endometrioide si de

obicei negativ in carcinoamele mucinoase); Ca125 +

CEA -


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Carcinom endometrioid IHC:

Keratin +

EMA +

Vimentin +

CEAsau slab +


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Tumori cu celule germinale: Tumora de sac yolk

IHC:

AFP+

Pankeratin +

CK 7

WT-

CEApattern canalicular cu Ac policlonal


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Carcinom embrionar : IHC :

hCG +

CK 7 + (pentru un subset de celule trofoblastice)

Teratom matur/imatur

IHC:

- GFAP + in structurile nervoase mature si imature (!poate

fi pozitiv si in condrocite)


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IHC utila uneori in diagnosticul diferential tumora primara/ tumora secundara ovariana

ex. Met. de ADK de colon

CK7-/ CK20+

CEA +

CA125

MUC 2 +

T. primara mucinoasa ovariana

- CK 7+- CK20 + focal, uneori

- CEA

- CA 125 +

- MUC 5AC+

!Atentie la carc. gastrice , pancreatice, etc

GGL limfatic


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NLPHL Celula popcorn

Pozitivitate pentru CD19, CD20, CD22, CD45RA,

CD45; Uneori pozitivitate pentru CD30 si EMA

CD15 negativ


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NHL


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SLL Arhitectura stearsa de o proliferare de limfocite

mici cu citoplasma putina, cromatina grunjoasa,nucleoli absenti si activitate mitotica redusa

IHC: CD20, CD22, CD19, CD79a +

CD5+

CD23+

CD43+

Ciclina D


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Limfom limfoplasmocitic Proliferare de limfocite mici, plasmocite si limfocite

plasmacitoide cu localizare im maduva osoasa simaduva hematopoietica

Prezenta de corpi Dutcher (pseudoincluzii nuclearePAS+)

IHC

IgM in citoplasma +

CD5-, CD10-, CD23- CD19, CD20, CD22, CD79a+

CD138+


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Mielom plasmocitar Maduva osoasa30% din volum ocupat de

plasmocite; corpi Russell;

IHC: CD79a, VS38c, CD138+

K, monoclonale

CD19

CD20, CD117, CD10 -/+


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Plasmocitom extraosos Localizare extramedulara; diagnosticul se pune

prin excluderea unui limfom MALT cu diferentiere

plasmacitoida


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Limfom folicular proliferare constituita din centroblaste/centrocite cu arhitectura foliculara, cel

putin partial

Foliculii neoplazici sunt slab definiti, cu zona de manta discreta sau absenta

Cele 2 tipuri de celule (centroblaste si centrocite) sunt difuz distribuite si nupolarizate, ca in centrii germinali reactivi;

Macrofagele cu corpi tingibili sunt de obicei absente

IHC:- CD19, CD20, CD22, CD79a +, IgM+/-

- bcl2, bcl6, CD10+

- CD5-

- CD21 si CD23detecteaza FDC

- gradul 3B poate fi lipsit de CD10, dar retine expresia bcl6

- bcl2- exprimat in 85-90% din LF gradul 1 si 2, dar in numai 50% dinlimfoamele grad 3


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Limfom de manta Proliferare limfoida monomorfa cu arhitectura difuza,

vag nodulara a zonei de manta sau, rar, foliculara;

Este alcatuita din celule mici sau medii, cu usoareneregularitati ale conturului nuclear (asemanatoare

centrocitelor) IHC

CD5, CD7, bcl-2, ciclina D1 +

sIgM/IgD+

Restrictie k/

CD10, bcl-6

Fenotipuri aberante: CD5-


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Limfom cu celule mari B difuz: Neoplasm cu celule B cu nucleu egal sau mai mare decat nucleul

macrofagelor sau mai mare de 2 ori decat al unui limfocit normal;

Etiologie: de novo sau prin progresia CLL/SLL, FL, MZL, NLPHL

Variante : centroblastica, imunoblastica, anaplazica (celule mari, cunuclei pleomorfi, bizari, asem cel S-R);

IHC:- CD19, CD20, CD22, CD79a +/-

- IgM>IgG>IgA

- CD30 + (varianta anaplazica)

- CD5 + (10% din cazuri)

- CD10 (30-60% din cazuri)

- bcl-6 + (60-90% din cazuri)

- ki-67>40%!!


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Limfom Burkitt Proliferare cu rata de dedublare f crescuta (mitoze

multe!), compusa din celule monomorfe cu

translocatie myc

IHC

CD19, CD20, CD22, CD10, bcl-6, CD38 +

Translocatie myc la regiunea IGH


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Limfom MALT = limfom de zona marginala extraganglionar

Mi: - limfom extraganglionar alcatuit din limfocite mici centrocitlike,celule centroblast like precum si imunoblaste, cu extensie in zoneleinterfoliculare In tes epiteliale, celulele infiltreaza epiteliul, generand leziuni limfoepiteliale;

IHC:

- IgM, CD20, CD79a +

- CD5, CD10, CD23, ciclina D1-

- ! Rareori CD5+

- CD21 si CD35 +, evidentiind retele de celule dendritice foliculare aflate infoliculii colonizati;

- restrictie de lanturi usoare /(prin care se face diagnosticul diferential cuinfiltrate limfoide benigne)

- abs CD5utila in diagn diferential cu MCL si CLL- abs ciclinei D1- utila in diagn diferential cu MCL

- abs CD10utila in diagn diferential cu FCL


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Limfom cu celule T periferice NOS IHC:

CD5, CD7, CD4, CD8+

CD30, CD15 + exceptional

Rearanjare TCR prezenta

Limfom anaplazic cu celule mari ALK pozitiv

IHC:

- CD30 + (marcaj membranar si golgian)- ALK+ (de preferat mAb)


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Limfom limfoblastic neoplazie constituita din celule precursoare

(limfoblaste) cu citoplasma redusa si cromatina

laxa sau condensata

IHC

CD19, cCD79a, cCD22, CD10+

Pax+

Tdt +

Tumori tesuturi moi


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T fibroase (fibromatoza, fibrosarcom) Contin fibroblaste, miofibroblaste si matrice

extracelulara (colagen si subst fundam)

IHC- vimentina, actina, desmin (in masura mai

mica), colagen


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T fibrohistiocitare Derivate probabil din fibroblaste;

Datorita lipsei markerilor specifici pentru acest lineaj,

diagnosticul se bazeaza pe lipsa markerilor pentru alte

lineaje ( DFSPCD34+++; neurofibromasS100);

Poate fi identificata imunoreactivitate pentru :

Vimentina, CD68, feritina, antitripsina

Focal: Keratine, desmina, NF (HFM angiomatoid exp desmina

in 50% din cazuri!)

Dgn de HFM este mentinut doar in 50% din cazuri


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T. de muschi neted SMA+ (mai sensibila)

Desmina+

Vimentina + Caldesmona:

pozitiva in leiomiom, leiomiosarcom, t. glomica

Negativa in t. rabdoide, t.desmoide

! Alti markeri (CK cu GM mica, S100, Leu-7 si chiar CD34 )pot fi

prezenti inconstantatentie la interpretare


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T. muschi striat:

Desmin

Actin sarcomeric

Miogenin (MyoD1)

Miozin

Mioglobin

Vimentin

Focal exprim: CK, protein S100 (in t. slab diferentiate) iprotein asociat neurofilamentelor

Ki-67factor important


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Sarcom Ewing extrascheletalPozitiv: Vim, CD99

Negativ: Des, Act, LCA, GFAP, Mio, ChrA

Tumor primitiv neuroectodermic

Pozitiv: CD99, NF, Syn

Negativ: markeri musculari

Condrosarcom mezenchimal

Pozitiv: CD99, S100, NSENegativ: CK, Des, Act, EMA, Syn


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Tumori ale tecii nervului: Neurofibromul:

Proliferare combinat de elemente ale nervului periferic

IHC

NSE + axoni

S100 + Schwann

Vim + fibroblaste

EMA + celule perineuriale

CD34 + celule ?


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Schwannomul

ncapsulat

IHC: S100, colagen IV, laminin, vim, rar CD68 i GFAP

Tip A

Celule fusiforme

Palisad

Corpi Verocay

Tip B

Arii edematoase

Spaii chistice

S100

Schwannom celular


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Tumora maligna a tecii nervului periferic: Pozitiv: S100 (50-70%), CD57 (50%), proteina

bazic a mielinei

EMA negativ, pan.CK +/-, CK7/19-

Diferenial: leiomiosarcom (S100), sarcom sinovial

(S100, CK7/19), melanom cu celule duziforme


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T. vasculare Hemangioendoteliomul :

Keratine, vim, CD31, +

CD34+/-

Angiosarcomul:CD31+

Limfangiom:

CD31, CD34, FVIIIrAg

Limfangiomiomul:Act, Des, HMB45


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Prostata AMACR (p504S)

Marker pozitiv al celulelor neoplazice si preneoplazice (PIN)util in diagn

P63, CK 34E12 (CK903), CK 5/6

- Markeri ai celulelor bazale, elimina diagn de leziune malignain leziuni precum atrofia si adenoza

! In prezent se face dublu marcaj p63-AMACR (p504S).

PSA are rol in diagnosticul tumorilor slab diferentiate

dezvoltate in regiunea cervico-prostatica precum si indiagnosticul tumorilor metastatice (! Poate fi neg dupahormonoterapie).

T genitale masculine


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Tumori cu celule germinale

Seminomul:

IHC:

PLAP+ (pozitivitate membranara in 90% din cazuri) C-kit (CD117)+

CD30, AFP, CK-


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Carcinomul embrionar: IHC:

CD30+

CK AE1/AE3, CK4,17,18,19+

PLAP + focal (membranar si/sau citoplasmatic)

AFP-

CD117-


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T de sac yolk IHC:

AFP+

CK+ (pozitivitate constanta, puternica)

CD117 + in aprox 80% din cazuri

CD30 -


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T de cordoane sexuale: IHC:

Inhibina, CD99, calretinina +

vimentina +

CK - sau cu pozitivitate variabila

IHC- interpretare.ppt

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