Markeri IHC in diagnosticul tumorilor epiteliale si conjunctive

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 (where lifespan 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

Bcl-2 in ggl limfatic

Bcl-2 in SLL

Bcl-2 in GIST

• BCL-6:
– encodes a 706 amino acid nuclear protein (repressor of p53), is rearranged in about 30% of diffuse large Bcell lymphomas, and is expressed predominantly in normal germinal center B cells and related lymphomas; – The antibody gives a strong nuclear labeling of BCL6 protein in follicular lymphomas, diffuse large B-cell lymphomas, Burkitt's lymphomas, and nodular, lymphocyte-predominance Hodgkin's disease.

Bcl-6 in ggl limf

Bcl-6 in limfom folicular

• ALK (anaplastic large cell lymphoma kinase)
– is a protein, 200 kDa, a transmembrane receptor tyrosin kinase, presumably receptor for the growth factor pleiotrophin. In normal tissues, ALK protein is expressed by only few cells within the developing and mature nervous system (glial cells, neurons, endothelial cells and pericytes); – ALK gene is translocated in ALCL, but also in inflammatory myofibroblastic tumor and in diffuse large B cell lymphoma (DLBCL).

• ALCL ALK in ALCL .

CD5 is also expressed in a small subset of normal human B-cells (20% of B-cells in the peripheral blood.• • • • CD5The CD5 antigen is a 67 kDa transmembrane glycoprotein expressed on the surface of practically all mature human T-cells (about 10% of CD4+ T-cells being CD5 negative). scattered cells in the lymph node mantle zone). CD5 is detected in 5% of acute myeloid leukaemias. • • • • . CD5 has been detected in some cases of thymic carcinoma and atypical thymoma. including 75% of peripheral T-cell lymphomas and 85% of T-ALL cases. CD5 is weakly expressed. the CD5+ B-cell population is expanded in rheumatoid arthritis and systemic lupus erythematosus. Among B-cell lymphomas. Lack of CD5 in the latter signifies a worse prognosis. marginal zone lymphoma and lymphoplasmacytoid lymphoma are CD5 negative. They also produce more autoantibodies than normal CD5 negative B-cells. The CD5+ cells are probably involved in B-T interaction and their ligand is CD72 which is expressed on all B cells. In immature (CD34+) Tcells. whereas follicular lymphoma. the intensity of expression increasing with maturation. Neoplasms CD5 is detected in most T-cell lymphomas and leukaemias. Thus. more explicit CD20+ small-cell lymphomas. It appears that CD5+ B-cells on activation primarily produce IgM. small lymphocytic lymphoma and mantle cell lymphoma are CD5+. Other carcinomas are CD5 negative.

CD5 in normal T cells CD5 in MZL .

– CD10 is found in almost all cases of endometrial stromal sarcoma. follicular lymphoma. follicular centre cells. but not chromophobic type) .• CD10 – CD10 is a single-chain cell surface glycoprotein. pulmonary alveolar cells. few mature Blymphocytes. 90-110 kDa. myoepithelial cells of breast. – small lymphocytic lymphoma. and mantle cell lymphoma. CD10 is found in some cases of diffuse large B-cell lymphoma. in most cases of hepatocellular carcinoma (distinct canalicular pattern). renal cell carcinoma (clear cell and papillary types. – CD10 is also found in enterocytes in the upper part of the intestinal tract (brush border. and lymphoplasmacytoid lymphoma are negative. kidney (glomerular and proximal tubular cells). – CD10 is expressed in most cases of precursor B lymphoblastic leukaemia/lymphoma. also designated common acute lymhoblastic leukaemia antigen (CALLA) – CD10 is present on the cell surface of bone marrow stem cells and myelopoietic cells (including neutrophils). marginal zone lymphoma.in liver (bile canaliculi). and Burkitt lymphoma.

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• Limfom folicular Carcinom renal .

lymphocyte depletion (LD) and lymphocyte rich-classical HD cases. and Langerhans' cells. but not in malignant cells of lymphocyte predominance (LP) HD (L&H cells. – It is expressed in great majority of nodular sclerosis (NS).• CD15 – a haematopoietic differentiation antigen expressed on most terminally differentiated myeloid cells including granulocytes. mixed cellularity (MC). monocytes/macrophages. “popcorn cells”) . – The positivity for CD15 is characteristic of Hodgkin’s cells in classical Hodgkin’s disease (HD). mast cells. eosinophils.

• CD15 in HD .

However. a special type of CD20 positive myelomas account for 10-20% of the cases. – CD20 appears on the surface of the pre-B lymphocyte between the time of light chain rearrangement and expression of intact surface immunoglobulin and is lost just before terminal B-cell differentiation into plasma cells. proliferation and differentiation. involved in the regulation of B-cell activation. – Early stage precursor B lymphoblastic leukaemia/lymphoma may be negative. . – CD20 is expressed in the large majority of cases of B-cell leukaemia/lymphoma. – Plasma cell neoplasms are as a rule CD20 negative.• CD20 – CD20 functions as a Ca2+-permeable cation channel. and chronic lymphocytic leukaemia/small cell lymphoma may show a weak staining.

• CD20 normal CD20 in CLL .

Leu-20. . .CD23 is typically expressed in chronic lymphocytic leukemia (CLL) .• CD23 . .!! CD23 is also frequently used to demonstrate benign follicular dendritic cells in the background of follicular lymphoma . monocytes. .In humans. main cellular expression of CD23 is found in B-lymphocytes (strong expression in activated germinal center B-cells.rarely in marginal zone and lymphoplasmacytic lymphoma.the strongest expression is characteristically present in proliferation centers. . weaker staining of resting mantle zone B-cells). FceRII. follicular dendritic cells (FDCs) predominately in the apical light zone of the germinal center. .not in mantle cell lymphoma.sometimes in follicular lymphoma.low affinity IgE receptor.

• CD23 in CLL .

anaplastic variant of diffuse large B-cell lymphoma (av-DLBCL). monocytes. anaplastic large cell lymphoma (ALCL). .• CD30 – CD30 is a member of the tumor necrosis factor receptor (TNF-R) superfamily. NK cells. – Expression of CD30 has also been demonstrated in embryonal carcinoma and some seminomas. – Some cases of mycosis fungoides can have significant CD30 expression. plasma cells. – CD30 is found in activated B lymphocytes. T lymphocytes. – CD30 is expressed in classical Hodgkin’s disease (cHD). and CD30 positive cutaneous lymphoproliferative disorder.

• CD30 in normal activated B cells CD 30 in HD CD30 in carcinom embrionar .

i. . – CD45 is lost in megakaryocytes and plasma cells. the L&H cells in the LP-type are always positive. and only about 10% of plasmacytic neoplasms are positive. – CD45 is expressed on cells of the human haematopoietic lineage with the exception of mature red cells.• CD45 – CD45 is a family of single chain transmembrane glycoproteins. – In Hodgkin lymphoma. while Reed-Sternberg cells in classic Hodgkin lymphoma are negative or only show a faint cytoplasmic staining.e. – CD45 has intrinsic tyrosine phosphatase activity and is essential for development and effector functions.. about 90% of malignant lymphomas are CD45 positive. The proportion is lower among precursor B-cell neoplasms (80% of B-ALL) and large cell anaplastic lymphomas. – It is not detected on differentiated cells of other tissues. playing an important role in signal transduction. – CD45 is detected in the large majority of haematolymphoid neoplasms. – Overall. inhibition or upregulation of various immunological functions. leukaemias and malignant lymphomas.

some epithelial neoplasms. epithelioid cells of some malignant melanomas . – Positive staining is seen in different types of macrophages of monocyte lineage and antibodies also reacts with myeloid precursor cells in the bone marrow. often with relation to lysosomes. localized in the cytoplasm.• CD68: – antibodies detect a glycoprotein with a molecular weight of approximately 110 kD. subtypes of myeloid leukaemia (depending on the Ab used). – Expressed in fibrous-histiocytic tumours and Langerhans cell histiocytosis.

• CD68 in celule Kupffer .

• CD31 – transmembrane glycoprotein. platelets. 130-140 kDa. angiofibroma. occasional plasma cells. – CD31 is strongly expressed in endothelial cells and weakly expressed in megakaryocytes. lymphocytes (especially marginal zone B-cells. hemangioma. peripheral T-cells) and neutrophils. belonging to the immunoglobulin super family. and angiosarcoma. – CD31 is expressed in the vast majority of all types of vascular neoplasms. – CD 31 is also expressed in most cases of Kaposi sarcoma . such as hemangioendothelioma. also designated platelet-endothelium cell adhesion molecule (PECAM-1).

• CD31 in hemangioendoteliom infiltrativ in intestin .

but is absent from large veins and arteries. gastrointestinal stromal tumor (strong positivity in about 80% of the cases. – CD34 is detected in myeloid blasts in myelodysplastic syndrome and acute myeloid leukaemia. lipoma (particularly spindle cell lipoma) and liposarcoma. – Also expressed in lymphoblasts in most cases of B-acute lymphoblastic leukaemia. only about 30% of the lymphangiomas are CD34 positive. – CD34 is found in most endothelia. solitary fibrous tumor. – CD34 positivity is seen in most cases of dermatofibrosarcoma protuberans.• CD34 – CD34 (also named myeloid progenitor cell antigen) is a heavily glycosylated type I transmembrane protein. including haemangiosarcoma and Kaposi sarcoma are CD34 positive . 110 kDa. role in adhesion. expressed on the luminal surface and membrane processes interdigitating between endothelial cells. – The majority of vascular tumours. which are also CD117 positive). . However. and a varying proportion of meningioma.

• CD34 in endothelial cells and precursor cells in BM CD34 in endothelial cells in placenta .

built up by more than 2000 aminoacids. the antigen can be demonstrated in a majority of. FVIII is often a part of the panel for the identification of benign and malignant vascular neoplasms. but not not all. cases – Due to the specificity of the antigen.• FVIII related antigen – Factor VIII-related antigen (FVIII) is the von Willebrand factor. along with CD31 and CD34. – This is tissue-specific and present only in endothelial cells. Kaposi sarcoma and Dabska tumour. a large protein. – In angiosarcoma. megakaryocytes and thrombocytes – FVIII is expressed in most tumours with endothelial differentiation. rather than the sensitivity. .

FVIII in hemangioendoteliom .

IC = Imperial Cancer Research Fund. 2 = order of discovery). also known as MIC2 (M = monoclonal. . solitary fibrous tumour. meningioma and T-cell acute lymphoblastic lymphoma/leukaemia. Most sex cord-stromal tumours are CD99+ .• CD99 – a 32kDa transmembrane glycoprotein.cell adhesion role – CD99 has been detected in almost all cases of Ewing's sarcoma/pPNET.

• CD99 in sarcom Ewing CD99 in tumora de granuloasa ovariana .

• CD117 – CD117 is a 145-160 kDa cell membrane protein encoded by the c-kit protooncogene (chromosome 4q11-12). – The cells (particularly the mast cells) show a strong membrane as well as cytoplasmic staining. cylindroma. malignant melanoma (however. – CD117 is expressed in mast cells. – CD117 moreover is expressed in various epithelia: breast. the expression of CD117 is lost during progression and metastasising). renal tubular cells. Merkel cell carcinoma. malignant glioma. endometrial carcinoma. thyroid follicular cells – The following neoplasms express CD117 in more than 90% of the cases: • Gastrointestinal stromal tumour (GIST) . melanocytes and interstitial cells of Cajal. mast cell neoplasms. and angiomyolipoma. . seminoma/dysgerminoma and intratubular germ cell neoplasia. sweat glands and salivary glands. follicular and papillary thyroid carcinoma. – The protein is a tyrosine kinase growth factor receptor for stem cell factor (SCF).

• CD117 in GIST CD117 in seminom .

– The CK family is a highly complex multigene family of polypeptides. 20 distinct CKs have been revealed (excluding the so-called trichocytic keratins present in hair and nail-forming epithelia only). 6.2 . the molecular weight of which ranges from 40 to 68 kDa. Until now. 5. 10. 5. AE3 directed to neutral-basic types CK1-8). The classification and numbering (CK1-CK20) is based on the catalogue of Moll et al. – Clone AE1/AE3 (AE1 directed to acidic types 9. 14. 8. clone MNF116 (directed to CK5. 17. 10. directed to LMWCK CK8 and CK7 . 13. – Clone CAM 5. 19) are broad spectrum cytokeratin antibodies useful for screening and visualisation of epithelial structures – Clone 34BE12 (directed to CK1. 6. 14 and an unknown CK subtype) is useful for detection of HMW CKs. 15. 8. 19) and clone KL1 (directed to CK2. 10. 18.• Cytokeratins – Cytokeratins (CKs) are intermediate filaments. 16 and 19.

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• P63 – p63 protein (p63) is a nuclear protein. myoepithelial carcinoma. more than 70% of the cases are positive) as well as adenosquamous carcinoma. as well as basal cells/myoepithelial cells in breast. salivary glands. and prostate – p63 is found in the large majority of cases of squamous cell carcinoma (even among low differentiated squamous carcinomas. adenoid cystic carcinoma and skin adnexal tumours . – p63 is confined to basal cells of squamous epithelia (including epidermis and hair follicles) and urothelium. The p63 gene is located at chromosome 3q27-29 and belongs to the p53 gene family. sweat glands. a transcription factor. urothelial carcinoma. – p63 plays a critical role in the growth and development of many epithelial organs.

• . A cocktail staining is applicable. However. p63 may enhance the ability to diagnose limited prostate cancer. • An important criterion for the diagnosis of prostate adenocarcinoma is the absence of basal cells. The same tumours are usually expressing cytokeratin 5. urothelial and myoepithelial differentiation. As these can be difficult to identify in routine sections. Since negative staining for high molecular weight cytokeratin (HMW-CK) in atypical prostate glands may not be sufficient for a definitive diagnosis of malignancy.• In carcinomas p63 is a very useful marker for squamous. p63 should be used in conjunction with HMW-CK and AMACR. p63 often shows a more extended reaction. However. immunohistochemical identification of p63 and cytokeratin 5 may increase the sensitivity and specificity. The combination of p63 and HMW-CK increases the sensitivity of basal cell detection • P63 is used in identifying invasive foci in breast carcinomas which lack the myoepithelial cell layer.

P63 in prostata normala .

and urothelium. esophagus. uterine cervix and ovary (mucinous type). CEA is expressed in the apical border and. esophagus and uterine cervix. biliary tract. small intestine. to a lesser extent in the cytoplasm. The prostate is negative (apart from urothelium lined secretory ducts). secretory epithelia of sweat glands. and stomach (surface epithelium. pancreas. of the columnar cells of colon. mucous neck cells and weakly in pyloric mucous cells). . – CEA is expressed in epithelial cell membranes and in the cytoplasm of the cells in almost all cases of colorectal adenocarcinoma as well as a high proportion of adenocarcinomas of the salivary glands. lung. – In normal adult tissue. pancreatic ducts. stomach. small intestine.• CEA – A glycoprotein comp of Ig superfamily (adhesion molecule). squamous epithelial cells of the tongue.

• CEA in colon normal .

prostate. pancreas. the mucinous type is almost always positive. – Among ovarian carcinomas. and thyroid. while varying positivity is seen in the other types. endometrium. In connecting cells they comprise a part of the zonula adherens and desmosomes. uterine cervix. – The following tumours are almost always positive: adenocarcinoma of colorectum. stomach. – Among breast carcinomas the ductal type (including the tubulolobular subtype) is almost always positive (at least in part of the tumour) while the lobular type is negative in 85 – 90 %.• Cadherins – Cadherins are a family of calcium-dependent transmembrane cell adhesion glycoproteins. .

E caderina in CDI .

related to the high molecular weight glycoproteins of human milk fat globule (HMFG). – The immunoreactivity is usually limited to apical cell membranes. EMA may be seen in anaplastic large cell lymphoma (50-95%). . EMA is demonstrated mainly in the long microvillous surfaces of the tumour cells with little cytoplasmic labelling – Among malignant lymphomas. diffuse large B-cell lymphoma. and prostate glands. and pancreas.• EMA (epithelial membrane antigen) – Epithelial membrane antigen (EMA. MUC1) is a group transmembrane proteins. whereas little or no EMA is expressed in the gastrointestinal epithelium. endocervical epithelium. plasma cell neoplasms (most cases). eccrine and apocrine glands. – EMA is present in a variety of glandular (secretory) epithelia such as breast. 40-425 kDa. but a staining of the Golgi zone may also be seen – EMA can be demonstrated in most types of adenocarcinomas derived from secretory epithelia – In malignant mesothelioma.

EMA in mezoteliom .

some neuroendocrine cells. – 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. hair follicular cells. eccrine sweat glands. endometrial stromal cells. testicular Leydig cells. rete testis. breast glands. thymic epithelial cells. ovarian theca interna cells). testicular Sertoli cells.• Calretinin – 32 kDa member of the superfamily of calcium-binding proteins. ovarian surface epithelium. . the protein is generally found in both the cytoplasm and nuclei. and fat cells – Calretinin is also expressed by both normal and neoplastic mesothelial cells. • it is an useful marker for the identification of malignant mesotheliomas of the epithelial type and for the differentiation of these malignancies of lung adenocarcinoma • In calretinin positive cells.

• Mezoteliom .

– encodes a transcription factor. which is involved in proliferation and differentiation of intestinal epithelial cells. – The CDX2 protein is widely expressed in intestinal epithelium from the duodenum to the rectum. a large part of gastric adenocarcinomas. urinary bladder and pancreas show CDX2 expression. including carcinoids .• CDX2 – Cdx2. – The majority of colorectal adenocarcinomas. carcinoids of the GI tract as well as adenocarcinomas of the ovary. Antibodies to CDX2 may be useful for identification of both primary and metastatic tumors of the gastrointestinal tract. a human homeobox gene.

endocrine tumor marker . 48-75 kDa. – Pan. – Chromogranin A (CGA). – Probably. is the diagnostically most important of these glycoproteins. these proteins are involved in packaging and processing of neuropeptides and peptide hormones. and probably the major target of the argyrophilic Grimelius staining reaction. 439 amino acids.• Cromogranin – chromogranins comprise a family of acid calciumbinding glycoproteins closely associated with the matrix of dense-core neurosecretory granules in virtually all neuroendocrine (NE) cells and neurons.

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and phaeochromocytoma/paraganglioma. ganglioglioma. and pituitary and parathyroid adenomas. small cell carcinoma. astrocytoma and ependymoma. – SYP may also be detected in other neural crest derived tumours like oligodendroglioma. central neurocytoma. carcinoid and neuroendocrine carcinoma. ganglioneuroblastoma. medullary thyroid carcinoma. – Also adrenal cortical tumours stain for synaptophysin. 38 kDa of presynaptic vesicles in all neurons and corresponding vesicles in all neuroendocrine (NE) cells – SYP is detected in virtually all neuronal tumours: Neuroblastoma.• Sinaptofizina – SYP is a calcium binding integral-membrane glycoprotein. – Moreover synaptophysin is detected in NE tumours like pancreatic islet tumours. . ganglioneuroma.

• Syn in carcinoid intestinal .

myofibroblasts and myoepithelial cells. The antibody recognizes rhabdomyosarcomas. leiomyosarcomas and pleomorphic adenomas . and is useful for the identification of leiomyomas. skeletal and smooth muscle cells as well as myoepithelial cells.• Actina. leiomyomas and leiomyosarcomas.clona 1A4 – This antibody labels smooth muscle cells. and also reacts with 'myofibroblasts' in the stroma of certain tumors including many carcinomas Actina .clona HHF35 – Labels myocardial.

LMS .• Actina.

• Caldesmon – a smooth muscle-specific protein involved in the regulation of smooth muscle contraction. • Calponin – a developmentally regulated protein thought to play a role in the regulation of the thin filamentassociated system of smooth muscle contraction. .

• Caldesmon in leiomiom .

g.• Desmin – Desmin is an intermediate filament protein (53 kDa) expressed in all striated muscle cells and most smooth muscle cells.. Desmin play no role in contractility but serves to maintain the orientation of actin and myosin filaments and may also play a role in nuclear transcription – Desmin is detected in most tumours of myogenic origin. leiomyosarcoma and rhabdomyosarcoma . e.

• Desmin in normal colon Desmin in LMS Desmin in carcinosarcoma .

and epithelial origin.• S100 – S100 is a 21kDa highly acidic and water soluble protein first isolated from brain but later shown to be produced by a wide variety of normal and neoplastic cells of mesodermal. Schwann cells and satellite cells. kidney). cytoplasm and nuclei. such as vimentin and Melan. and follicular dendritic cells. a negative staining is exceedingly rare. some glandular epithelia (breast. melanocytes. Because of its low specificity. fat cells and chondrocytes. myoepithelial cells. other markers should be included in a panel for malignant melanoma. skeletal and heart muscle cells.A. – The immunohistochemical evaluation of S-100 (beta) protein expression is important in the diagnosis of undifferentiated malignant tumours of unknown primary origin and should be included in the so-called primary panel. – S100 (beta protein) is present in glial cells. neuroectodermal. – S100 is a very sensitive marker for malignant melanoma of all types. – S-100 protein may be found in the cell membranes. .

Vimentin is expressed in a wide variety of mesenchymal cell types fibroblasts. macrophages etc.g. Also thyroid carcinomas are vimentin positive. vimentin is often replaced by desmin. e. in non-vascular smooth muscle cells. during regeneration. endothelial cells etc.g. angiosarcoma. Sarcomas e.• • • • • • • Vimentina Vimentin (57 kDa) is the most ubiquituos intermediate filament protein and the first to be expressed during cell differentiation. vimentin is reexpressed. adrenal cortical carcinoma and adenocarcinomas from endometrium and ovary usually express vimentin. e. However. sometimes in scarce amounts.. an in thyroid gland epithelium Vimentin is present in many different neoplasms but is particulary expressed in those originated from mesenchymal cells. in myoepithelial cells (breast. Mesoderm derived carcinomas like renal cell carcinoma. as well as lymphomas. vimetin is also replaced by desmin. Vimentin is also found in mesoderm derived epithelia. All primitive cell types express vimentin but in most non-mesenchymal cells it is replaced by other intermediate filament proteins during differentiation. malignt fibrous histiocytoma. kidney (Bowman capsule).and rhabdomyosarcoma. However. and in a number of other cell types derived from mesoderm. fibrosarcoma. salivary and sweat glands). mesothelium and ovarian granulosa cells. Cells of the lymfo-haemopoietic system (lymphocytes.. • • • • .) also express vimentin. malignant melanoma and schwannoma..g. endometrium and ovary (surface epithelium). In striated muscle. are virtually always vimentin positive . Any low differentiated or sarcomatoid carcinoma may express some vimentin. and leio.

Vimentina in limfocite din amigdala Vimentina in glanda mamara .

and neuroendocrine tumours like medullary thyroid carcinoma. NFP is represented in virtually all neurons. 160 kda and 200 kDa. carcinoid. etc. in some cases of primitive neuroectodermal tumour (neuroblastoma etc. Merkel cell carcinoma. and small cell carcinoma. phaeochromocytoma/paraganglioma... – NFP can be demonstrated in the large majority of differentiated neuronal tumours: ganglioneuroma. ganglioneuroblastoma.). 70 kda.• Neurofilamente – NFP is a class 4 intermediate filament protein comprising three heteropolymeric polypeptide units. .

NF in meningiom NF in neurofibrom (cel Schwann si fibroblaste neg) .

– Nuclear expression of MyoD1 is restricted to skeletal muscle tissue and has been demonstrated to be a sensitive marker of myogenic differentiation. – MyoD1 immunostaining has been demonstrated in the majority of rhabdomyosarcomas of various histological subtypes. whereas the majority of adult skeletal muscle is negative. – The antibody strongly labels the nuclei of myoblasts in developing skeletal muscle tissue. .• Myo D1 – The MyoD1 protein is a 45 kDa nuclear phosphoprotein which induces myogenesis through transcriptional activation of muscle-specific genes.

– The antibody recognizes an epitope located in the amino acid region 138-158 of the myogenin protein.• Myogenin – Myogenin belongs to a family of regulatory proteins essential for muscle development. and appears to be inversely related to the degree of cellular differentiation. – It labels nuclei in the majority of human rhabdomyosarcomas and Wilms' tumors . – Expression of myogenin is restricted to cells of skeletal muscle origin.

• Myogenin in rabdomiosarcom .

coelomic and mullerian epithelium. – CA125 is expressed in almost all cases of (epithelial) malignant mesothelioma and ovarian serous adenocarcinoma – CA125 is also expressed in the majority of primary peritoneal carcinoma and ovarian clear cell and endometrioid adenocarcinomas. endometrium and endocervix. – In foetal tissue.• Cancer antigen 125 (CA125) – is a membrane mucin-like glycoprotein greater than 200 kDa. – In adult tissue CA125 is primarily expressed in mesothelial cells and in the luminal surface of epithelial cells of the fallopian tube. . CA125 is expressed in the amnion. The specific function is unknown.

• CA-125 in mezoteliu Ca125 in mezoteliom CA125 in carcinom ovarian .

• AFP (alfa feto protein) – a 70 kDa glycoprotein, synthesized by the cells of the embryonic yolk sac, fetal liver and fetal intestinal tract. – Expression of AFP has been demonstrated in many hepatocellular carcinomas and in gonadal and extragonadal germ cells tumors, including yolk sac tumors. – The antibody may be useful for the identification of non-neoplastic and neoplastic liver diseases, yolk sac tumors and mixed germ cell tumors

• AFP in tumora sac yolk

• Estrogen receptor
– Estrogen receptor (ER) belongs to the steroid receptor superfamily of nuclear receptors; – ERα is mainly expressed in tumours of female sex steroid hormone responsive tissues such as :
• the mammary gland, endometrium, and ovary. • ERα protein is expressed in 60-70% of female breast cancers • Other tumours expressing ERα are meningiomas, salivary gland tumours, some neuroendocrine tumours, and some colorectal and hepatocellular carcinomas.

• ER in adenoc uterin ER in sarcom stromal uterin ER in tumora pancreatica .

c-erbB2. HER-2 is over-expressed in 15-25% of primary breast cancers. Of the histologic types.) of the cells. its activation causes malignant transformation and increases the malignant potential (cell proliferation. invasiveness etc. whereas only a small minority of lobular and tubular carcinomas shows HER-2 amplification. ERBB2 or neu) is a transmembrane receptor tyrosine kinase. – HER-2 is a proto-oncogene. which is a genomic mutation where a small fragment at chromosome band 17q12-q21 is multiplied in a cell up to 50-100 folds. Metastases usually have the same amplification status as the primary tumours. HER-2 amplification and over-expression are typical features of hormone receptor negative. – In tumours. ovarian carcinomas.• Her 2 – HER-2 (also called HER-2/neu. high grade endometrial carcinomas and some salivary duct tumours . Paget’s disease is almost invariably HER-2 positive. In human cancers HER-2 is activated via gene amplification. rapidly growing histologic grade 2-3 tumours. which was originally discovered from a rat neuroblastoma cell line (named “neu”) more than 20 years ago. i. – HER-2 amplification and over-expression can also be found in intestinal type gastric and gastroesophageal carcinomas.e.

it is expressed in cells of premalignant highgrade prostatic intraepithelial neoplasia (HGPIN) and prostate adenocarcinoma (1). .In glandular epithelial cells of normal and benign hyperplastic prostates AMACR is present at low or undetectable levels. .AMACR (P504S): . .is an enzyme that is involved in bile acid biosynthesis and β-oxidation of branched-chain fatty acids.

AMACR in carcinom prostatic .

– PSA is strongly expressed in both normal and neoplastic prostatic tissue . – It is primarily produced by the prostatic epithelium and the epithelial lining of the periurethal glands.• Prostate-specific antigen (PSA) – is a 33 kDa protein belonging to the kallikrein family of proteases.

• PSA in carcinomul de prostata .

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usually a widespread reaction). mixed mullerian tumour. while WT1 is not found in endometrial or cervical epithelium. stromal and blastemal elements). As regards nonepithelial cells. a DNA-binding nucleoprotein. nuclear WT1 expression is largely restricted to ovary (surface epithelium and inclusion cysts) and fallopian tube. nuclear WT1 is strongly expressed in the large majority of malignant mesothelioma and sex cord-stromal tumours.• WT-1 – The WT1 gene located at chromosome 11p13 codes for a transcription factor. that plays a role primarily in the development of genitourinary organs. . and about half of ovarian endometrioid carcinoma (grade 2 and 3 but not grade 1). endometrial stromal sarcoma. nuclear WT1 is strongly expressed in ovarian serous carcinoma (97% of the tumours. – In normal epithelia. as well as in some malignant lymphomas (lymphoblastic and Burkitt's lymphoma). and most cases of acute leukaemia. ovarian transitional carcinoma. uterine leiomyosarcoma. involving epithelial. Also metanephric adenoma is positive – Among nonepithelial tumours. – Nuclear WT1 has moreover been demonstrated in Wilms' tumour (about 50% of the cases. peritoneal serous carcinoma. 52-62 kDa. nuclear WT1 is found in mesothelium and some submesothelial stromal cell – Among epithelial tumours. malignant rhabdoid tumour. adenomatoid tumour.

WT-1 in mezoteliul normal WT-1 in mezoteliom .

. staining is also seen in steroid hormone producing cells: adrenal cortex . melanotic neurofibroma. – Using the monoclonal antibody A-103. – In metastastic melanomas the staining may be patchy and somewhat less often positive than in the corresponding primary tumours. melanosome producing). staining is furthermore seen in steroid hormone producing tumours: adrenocortical adenoma and carcinoma . – In desmoplastic melanoma the staining reaction is frequently patchy or negative. sex cord-stromal tumour of the ovary and Leydig cell tumour of the testis. This is due to cross reaction (as the Melan-A gene is not detected in these cells). including all primary cutaneous malignant melanomas and mucosal melanomas. lymphangioleiomyoma(-tosis). recognized by autologous cytotoxic T lymphocytes. derived from modified smooth muscle cells in the so-called tuberous sclerosis complex: angiomyolipoma. Melan-A is also called MART-1 (melanoma antigen recognized by T cells). melanotic schwannoma and other melanotic neural crest derived tumours. granulosa and theca cells of the ovary and Leydig cells of the testis. – Melan-A is also demonstrated in other tumours of melanocytic origin or differentiation (i.• Melan-A – Melan-A is a melanocyte differentiation antigen. as well as in so-called PEComas (perivascular epitheloid cell tumour. such as clear cell sarcoma.. – Melan A is expressed in 80-100% of malignant melanomas. – Using the antibody A-103. and pulmonary sugar tumour.e.

Melan A in epiteliul normal Melan A in melanom .

but also here Melan-A may give a stronger staining. spindle cell and desmoplastic malignant melanoma are MSA negative or only focally positive – Being a highly specific marker. – MSA is useful for the identification of PEComa (together with alpha smooth muscle actin). However. 10 kDa. Black). detected by the monoclonal antibody HMB-45 (Human Melanoma. However. MSA is generally a less sensitive marker than Melan-A and microphthalmia transcription factor (Mitf). particularly in the dermal component of benign melanocytic tumours and in spindle cell melanoma. .• HMB-45 – Melanosoma antigen (MSA) is an incompletely characterized oligosaccharide side chain of a glycoconjugate. – Malignant melanoma are MSA positive in most cases (60-90%). MSA has been widely used for the identification of melanocytic differentiation.

HMB-45 in melanom – pattern punctiform .

depending on the clone used – Small cell lung carcinoma express TTF1 almost consistently.e.. TTF1 is seen in virtually all tumours of follicular derivation. typical and atypical carcinoid and large cell neuroendocrine carcinoma do so variably. – Most anaplastic thyroid carcinomas have been reported negative. – Also the C-cell derived medullary carcinomas are positive for TTF1 immunoreactivity in virtually all cases (lower frequencies in some studies being possibly due to technical causes). TTF1 is widely expressed in pulmonary adenocarcinomas. – Among lung neoplasms. about 90%. follicular adenoma and follicular and papillary carcinoma. according to the literature 0-95% being positive! . i.• TTF-1 – TTF1 was first identified as a thyroid-specific DNA-binding activity which interacted with the rat thyroglobulin gene – Among thyroid neoplasms. while other pulmonary neuroendocrine tumours. the frequency of positive tumours being 60-85%.e. i.

inhibin α is a sensitive marker for the majority of sex-cordstromal tumors. • In abnormal ovarian tissues. • It is produced by ovarian granulosa cells and inhibits the production or secretion of pituitary gonadotropins.• Inhibin is a dimeric glycoprotein hormone comprised of an α and a β subunit. • The antibody was raised against the terminal 1-32 amino acid sequence of the inhibin α subunit. . particularly follicle-stimulating hormone.

TTF-1 in carcinom tiroidian folicular .

– It is synthesized by thyrocytes and transported to the apical surface where it is secreted into the lumen of thyroid follicles and stored as the major component of colloid. – The antibody is useful for the detection of thyroglobulin in thyroid tissue and is a useful tool for the identification of well-differentiated thyroid carcinomas .• Thyroglobulin – is the precursor of thyroid hormones.

Tireoglobulina in carcinomul papilar tiroidian .

G2 and M-phases). but absent in resting cells (G0-phase).• The Ki-67 antigen is a large nuclear protein (345. S. • 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 . 395 kDa) preferentially expressed during all active phases of the cell cycle (G1.

Ki-67 in mucoasa colonica normala .

– S-100 . pozitiv de asemenea in dermatofibrom si tumori de muschi neted. dar cel mai putin folositor (nespecific). – !! Un nr semnificativ de melanoame este poz la keratine cu greutate moleculara joasa (Cam 5. implicata in sistemul tirozinazic de producere a melaninei) si este. EMA. in diagn dif cu metast de carc de gl mamara S100 poz). HMB-45. – HMB-45 mult mai specific. Melan-A. dar mult mai folositor (negativ in multe tumori cu care se face diagn. – Tirozinaza – pozitiva in peste 90% din cazuri. S-100. testicul sin tumorile care au originea in acestea. prin urmare.poz in aprox 80% din aceste tumori. tirozinaza si MTF (microftalmia transcription factor). – Melan A (MART-1).antigen de diferentiere melanocitara. . – Vim – cel mai consistent marker (prezent in 100%din cazuri) . dar mai putin sensibil decat S-100 (util de ex. de asemenea nespecific. ovar. alfa1 antichimotripsin si CD68.2). recunoaste o glicoproteina premelanosomica (g100).• Melanomul tipic: – Pozitiv: vimentin. altele sunt pozitive la CEA. – MiTF – proteina nucleara necesara in viabilitatea melanocitara – marker al majoritatii melanoamelor conventionale. neg in melanoamele nepigmentare si in melanomul desmoplastic. poz de asemenea in celulele de corticosuprarenala producatore de hormoni steroizi. neg in melanoamele desmoplazice. alte tumori pozitive: MPNST si tumorile endocrine. diferential).

HMB-45 Vimentina .

• Melan A (Mart-1) .

. nuclei rotunzi.• Carcinom cu celule Merkel: – Aspect monomorf . VIP… Diagn. • Enolaza neuron specifica • Cromogranina. stroma cu numeroase vase cu endoteliu inalt – IHC : poz pentru: • citokeratine cu greutate mica (CK 20. numerosi nuclei fragmentati. cromatina in “sare si piper”. celule cu citoplasma putina . perinuclear. vacuolati. Diferential cu carc neuroendocrin cu cel mici de plaman (CK7 poz si TTF poz). rar intalnit in alte organe) • Neurofilamente. nucleolati.aspect punctiform. sinaptofizina.

.

miozina.• HFB Pozitiv : • Vimentin • FXIIIa .CD34 (care este poz in DFSP) .De multe ori poz la markeri de muschi neted (actina. desmina).!! Confuzie cu tumori de muschi neted!! Negativ: .

FXIIIA

• DFSP:
– Neoplasme cu crestere nodulara, polipoida, care se dezvolta in derm si de unde invadeaza tesutul subcutanat; – Arhitectura storiforma, celularitate crescuta, activitate mitotica moderata spre crescuta, lipsa CGM, inglobarea celulelor adipoase – IHC – pozitiv pentru - CD34!!
• - actina, vimentina

– IHC – negativ pentru : S100, HMB-45, keratine, FXIIIa
• Bednar tumor(pigmented DFSP) – neg for S100

CD34 in DFSP

CD31.. – IHC – celulele fuziforme sunt probabil celule mezenchimale nediferentiate sau care manifesta tendinat de diferentiere spre celula endoteliala.• Sarcom Kaposi: – Mi: celule fuziforme ce formeaza fante ce contin hematii ce se intrepatrund cu macrofage. factori de adeziune vasc. FXIIIA. de aceea sunt poz la : FVIII-related antigen. etc. . limfocite. CD34.

3 si MOC-31 (poz in adenoc) . CK 5/6 si WT1. EMA – neg: CEA.Plaman si pleura • Mezoteliom – AA pozitiv/ PAS negativ – IHC – poz pt. B72. : calretinin.

• Calretinin EMA – pattern membranar .

CEA – P63. Adenocarcinom pulmonar . CEA ! Cateodata vimentin +CK .EMA.EMA. p53 ( mutatia apare in stadii timpurii).TTF-1 .S100 prez in celulele Langerhans din stroma .LMW keratins (CK 7 +/ CK 20 neg) .• Carcinom scuamos pulmonar: – CK de greutate mica si mare – Vimentin.

TTF in adenoc pulmonar .

keratine. nucleoli absenti. sinaptofizina. citoplasma putina. IHC: .neg (dgn dif cu PNET/ sarcom Ewing) TTF – poz in aprox. CD99 . diferential cu ADK). .pozitivitate variabila pentru : neurofilamente. cromogranina. hipercromatici. Leu-7. Carcinomul cu cel mica: .• Carcinom cu dezvoltare lepidica (fostul carcinom bronhiolo-alveolar) – !! Subtipul mucinos este CK 20 poz si TTF-1poz – MUC3 si MUC6 poz ( diagn.caracteristic: nuclei “mulati”. 85% de cazuri. cromatina fina. mitoze numeroase ( posibil ca aceasta celula apare din celule epiteliale si in cursul tranformarii maligne sufera diferentiere endocrina). enolaza neuron specifica (marker seric de asemenea!).

syn. – Neurofilam – Leu-7 – LMW CK (Ck 7+/ CK 20 -) – TTF-1 (poz in 85% din cazuri).• Carcinom pulmonar cu celula mica – Markeri neuroendocrini : crg. . NSE.

.

citoplasma putina.apare din celule Kulchitsky .TTF poz ! Carcinoid atipic – hipercromazie. monomorfe.celule mici. fin granulara.CK 7+/ CK 20 neg . IHC – markeri identici cu carc cu cel mica + diferiti hormoni (VIP. arhitectura cordonala sau insulara.• Carcinoid . activit mitotica (2-10/10HPF) . necroza. ACTH…) . rar papilara. nuclei centrali.

Sinaptofizina .

focal S-100.• Tumora cu celule clare (sugar cell tumor) – HMB-45. enolaza. – Metastaze! . sinaptofizina.

– Alti markeri poz: S100.Tiroida • Carcinom papilar tiroidian – CK 7+/CK 20 – – CK19 + – HMW CK 34betaE12 + – Tireoglobulina. EMA. ER. HBME-1. . CEA. galectin. TTF-1 + (intensitate mai scazuta de obicei decat in carc folicular).

tiroglobulina + – LMW keratins. EMA. HMB45+ • !! CK14 . laminina – Tumori cu celule oncocitare: • TTF-1. tiroglobulina + • CEA. S100.• Carcinom folicular tiroidian: – TTF-1.specific .

TTF in carc folicular tiroidian metastatic .

somatostatina. .• Carcinom medular – TTF-1+ – Markeri pan-endocrini + – Calcitonina!! – Keratine. CEA – ACTH..

Calcitonina in carcinom medular tiroidian .

– MUC5AC+: tip difuz. EMA. – CK7 + (70% din cazuri). LMW CK + ( dar cateodata CK13.Tract digestiv • Gastric carcinoma – MUC-1+: tip intestinal. – CK20 + (20%). – Hepatoid ADK: Hep. (cardia) – MUC2+ : tip mucinos – CEA.Par-1+ si AFP + . 16).

CK7 CEA .

• Tumori stromale gastrice: – Origine: celule Cajal. cu rol in coordonarea activitatatii contractile a muschiului neted. – IHC : • CD117 + • CD34 + • Ki-67 . celule de origine mezodermica.

CD117 .

mai rar insulara • Nuclei regulati si normocromatici. SYN. vascularizatie bogata. CRG. keratine . IHC : . necroza absenta.NSE.• Tumori cu celule endocrine – WDNET (tumora endocrina bine diferentiata su carcinoid) : • arhitectura microglandulara. rare mitoze. trabeculara.

. mitoze (>2%).• Carcinom neuroendocrin bine diferentiat – Aceleasi caracteristici microscopice + trasaturi de atipie: necroza. caracter invaziv – Aceiasi markeri neuroendocrini Carcinom 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 .

– Markeri neuroendocrini: Syn.Intestin subtire • Tumori endocrine: – Origine in celulele endocrine ale glandelor Lieberkuhn. PGP9. NSE. – Pozitivitate: CEA. Leu7. .5. CK20 (20%). CK7(10%). CRG.

. infiltrat inflamator cu limfocite Tc (CD3 si CD8 pozitive) in corion si intraepitelial.• Boala celiaca (sprue) – Atrofia vilozitatilor.Generata de Tropheryma whipelii.Mi: plaje de macrofage in lamina propria ce determina distorsiuni arhitecturale ale vilozitatilor intestinale si care contin in citoplasma material PAS pozitiv datorita bacililor. – !sprue refractar se caracterizeaza prin prezenta LT gamma delta Boala Whipple . . .IHC : CD4/ CD8 LT scazut.

• GIST • ADK • Limfoame

• 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 polipii hiperplazici si adenomatosi si chiar si in mucoasa normala).

CDX2 – nuclear marker

– Carcinom mucinos: • MUC-2 poz Carcinom cu celule in inel cu pecete .Carcinoame endocrine si mixt . .CK7-/CK20+ (origine in colon) versus CK7+/CK20(stomac).

• GIST • Limfoame .

GCDFP+/. CK20+/-.( pattern diferit de adenocarcinomul clasic care este CK7-).HPV Boala Paget: CK7 poz. Melanom .• Canal anal – Carcinom scuamos • IHC.

2) si CK7 (intr-un nr mic de cazuri). Hep-Par-1 (mAb ce interactioneaza cu o proteina citoplasmatica inca necunoscuta prezenta in hepatocite normale si neoplazice). • Tumorile bine diferentiate: laminina. EMA. • MOC31 –negativ (pozitiv in colangiocarcinom si metastaze hepatice). • CEA –negativ sau focal pozitiv (ajuta in diagnosticul diferential pentru ca este pozitiv in carcinomul de cai biliare si in carcinoame metastatice) ! Pozitivitate de tip canalicular! • Pozitivitate de asemenea la ER si AR. . ceea ce nu se intampla pentru sinusoidele hepatice. keratine: CK8 (CAM 5.• Ficat: – Carcinom hepatocelular: • Pozitivitate pentru : AFP. fibonectina • Vasele sunt pozitive la CD34.

CK-7 CK-8 .

• Colangiocarcinom – Coloratie pentru mucina pozitiva (!) – IHC.pozitivitate pentru CEA (pozitivitate citoplasmatica si luminala !). AE1/AE3 (HMW CK). – Profilul CK in colangiocarcinomul intrahepatic (CK7+/CK20+) este diferit fata de colangiocarcinomul extrahepatic (CK7+/CK20-) . Cam 5. EMA.2 (LMW CK).

alti markeri endoteliali. HMB-45. Angiomiolipom .• Tumori mezenchimale – Angiosarcom • Pozitivitate: FVIII related antigen. desmina. . S100.Pozitivitate la : actina.

• FVIII related antigen .

diferential cu carcinomul papilar intraductal. 15. 19.3 • MUC1 (dgn. B72. CA19-9. 5/6. 17. 18.8.pozitivitate pentru: • EMA. 20. carcinomul ampular si cel mucinos) . 10. keratine (CK 7.• Pancreas – Adenocarcinom ductal. 13) • CEA.

B72. syn. inhibina si Melan A – Negativitate pentru: cromogranina – Pozitivitate de asemenea pentru calretinin (focal). keratine ( in special adenoamele. CEA. bcl2.Glanda suprarenala • Tumori de corticosuprarenala (adenom/carcinom de corticosuprarenala): – Pozitivitate pentru : vimentina. – Negative pentru :EMA. focal si sporadic) – !!Adenoamele au expresie mai scazuta pentru vimentina si mai crescuta pentru LMW CK.3 .

RCC. CD10 . CK. EMA. renal: pozitivitate pentru vimentina.• Adenom de corticosuprarenala versus carcinom renal: – C.

neurofilamente. alte peptide vasoactive . serotonina. sinaptofizina. cromogranina. gastrina.celule sustentaculare: pozitive la S100 .• Tumori de medulosuprarenala ale adultului – Hiperplazie de medulosuprarenala – Feocromocitom IHC: .pozitivitate pentru catecolamine. NSE.

.inhibitor de CDK inactivat de HPV-E7. • exista leziuni de grad inalt p16 negative !!! • KI-67 – in mod normal prezent numai la nivelul stratului parabazal. in CIN II – indica rata de proliferare inalta.Cervix – CIN Tract genital feminin • P16. in CIN III – prezent in toata grosimea epiteliului.in leziunile CIN II si CIN III mai mult de jumatate din grosimea epiteliului prezinta pozitivitate (2/3 -1/1). ceea ce implica ca supraexpresia P16 indica prezenta HPV de risc inalt.

negativitate sau prez slaba pentru ER.• Carcinom scuamos invaziv – Pozitivitate pentru : • Keratine • P63 • CEA Adenocarcinom endocervical: -! Coloratii histochimice si marcaje IHC pentru mucina poz (prez difuz intracelular) . endometrioid de endometru! (atentie la carcinomul seros de endometru care este pozitiv la p16) . PR -HPV prezent (col IHC pentru HPV sau p16) Toate acestea ajuta la diagnosticul diferential cu adenoc.negativitate pentru vimentina .pozitivitate pentru CEA .

Serotonin .CEA .Syn + .keratine .• (Adeno)carcinom mezonefric: • CD10+ • Calretinin + Carcinom neuroendocrin .NSE + .Cromog + (cazurile bine diferentiate) .

8. 18. • !WT-1 pozitiv in carc papilar seros ovarian si neg in carc papilar seros de endometru si alte carcinoame primare de endometru . urmat de carcinomul papilar seros si carcinomul cu celule clare). 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 .• Uter – Adenocarcinom endometrioid: • Keratine 7. PR. • ! Carc adenoscuamos de grad inalt este neg la ER.

.• Tumori stromale uterine – Mi • Constit din celule mici uniforme.S100 - . invelite de fibre de reticulina.CD10 + .IHC: . • Absenta vaselor mari cu perete gros • Przenta spatiilor de clivare . PR + . unele cu pereti hialinizati. asem celor din stroma endom.actin + (de obicei) . • Focare de hialinizare si izolate celule spumoase.vimentina + .h-Caldesmon – .Desmin. • Arhitectura multinodulara • Arteriole spiralate. -/ + (uneori prez. focal).ER.

h-Caldesmon poztive pe ariile “starbust ” .• Tumori combinate musculare si stromale (stromomioma): – MI – aspect caract de “starbust ” a componentei musculare netede – IHC : CD10+ – Desmin.

• Tumori uterine similare tumorilor ovariene cu origine in cordoanele sexuale: – IHC: • CD99 + • Inhibin + .

– Pot fi intalnite elemente scuamoase. . slab diferentiate. celula clara sau papilar seros) si elemente sarcoma-like homologe (de tip fibro sau leiomiosarcom) sau heterologe ( condro sau osteosarcom).• Tumori mixte mulleriene maligne: – Aspect mixt constituit din elemente carcinomatoase (de tip glandular : endometrioid.

dar si .• IHC : – Keratine + (in ariile epiteliale.in aprox jumatate din cazuri. – CD10 + in componenta sarcomatoasa – Her2 neu + .in componenta sarcomatoasa).

desmin. calponin. PR + ( cu intensitate mai mare in leiomioame decat in leiomiosarcoame).• Tumori de muschi neted (leiomiom/leiomiosarcom) – Actina. . h-caldesmon + – Vimentin+ – LMW keratins (CAM 5.2)+ (de obicei) – ER.

B72. mai putin carcinoamele endometrioide si de obicei negativ in carcinoamele mucinoase). 18. 19.• Ovar – Tumori epiteliale seroase • IHC – – – – – CK7+ CK20CK . borderline WT-1+ difuz in carcinoamele seroase (la fel in mezotelioame peritoneale. EMA.3 + S100 + in special in t. – Ca125 + – CEA - .

maligne si de tip intestinal) Keratine + EMA (in special cele maligne)+ CK 7+ in toate cazurile CK20+ aprox 50% din cazuri .• Tumori epiteliale mucinoase – IHC: • • • • • CEA + (in special t.

• Carcinom endometrioid – IHC: • • • • Keratin + EMA + Vimentin + CEA – sau slab + .

• Tumori cu celule germinale: – Tumora de sac yolk • IHC: – – – – – AFP+ Pankeratin + CK 7 – WTCEA – pattern canalicular cu Ac policlonal .

• 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) .

de granuloasa: IHC: .vimentin + .CD99 + . cu pattern punctat) .! Pozitivitate intensa si difuza citoplasmatica pentru keratine indica carcinom!! .desmoplakin + .inhibin + .SMA + .CK8.S100 + in aprox 50% din cazuri .• Tumori de cordoane sexuale: T.EMA – . 18 + ( in aprox 1/3 din cazuri .

CEA – . Met.• IHC utila uneori in diagnosticul diferential tumora primara/ tumora secundara ovariana – ex. de ADK de colon • CK7-/ CK20+ • CEA + • CA125 – • MUC 2 + T. etc . gastrice .CK 7+ . primara mucinoasa ovariana .CA 125 + .MUC 5AC+ !Atentie la carc. uneori . pancreatice.CK20 + focal.

GGL limfatic • NLPHL – Celula popcorn – Pozitivitate pentru CD19. CD22. – Uneori pozitivitate pentru CD30 si EMA – CD15 negativ . CD45. CD45RA. CD20.

difuz citoplasmatic sau membranar) – in peste 80% din cazuri – CD30 + in aprox 90% din cazuri. – CD45+ in mai putin de 10% din cazuri. – CD45RO si CD43 +in mai putin de 10% din cazuri .GGl Limfatic • HL clasic – celula RS – CD 15 + (pattern golgian. – CD20+ in 10-20% din cazuri.

• NHL .

CD19. cromatina grunjoasa.• SLL – Arhitectura stearsa de o proliferare de limfocite mici cu citoplasma putina. CD79a + CD5+ CD23+ CD43+ Ciclina D – . CD22. nucleoli absenti si activitate mitotica redusa – IHC: • • • • • CD20.

• Limfom limfoplasmocitic – Proliferare de limfocite mici. CD10-. plasmocite si limfocite plasmacitoide cu localizare im maduva osoasa si maduva hematopoietica – Prezenta de corpi Dutcher (pseudoincluzii nucleare PAS+) – IHC • • • • IgM in citoplasma + CD5-. CD23CD19. CD79a+ CD138+ . CD20. CD22.

CD10 -/+ . CD117. λ monoclonale CD19 – CD20. corpi Russell. VS38c. – IHC: • • • • CD79a.• Mielom plasmocitar – Maduva osoasa – 30% din volum ocupat de plasmocite. CD138+ K.

• Plasmocitom extraosos – Localizare extramedulara. diagnosticul se pune prin excluderea unui limfom MALT cu diferentiere plasmacitoida .

exprimat in 85-90% din LF gradul 1 si 2.CD19. dar in numai 50% din limfoamele grad 3 . CD10+ . 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 nu polarizate. bcl6.• Limfom folicular – proliferare constituita din centroblaste/centrocite cu arhitectura foliculara. CD22. – Macrofagele cu corpi tingibili sunt de obicei absente IHC: . CD79a +. CD20.bcl2. IgM+/.CD5. ca in centrii germinali reactivi. dar retine expresia bcl6 .CD21 si CD23 – detecteaza FDC .bcl2.gradul 3B poate fi lipsit de CD10.

cu usoare neregularitati ale conturului nuclear (asemanatoare centrocitelor) – IHC • • • • • CD5. – Este alcatuita din celule mici sau medii. rar. bcl-2. ciclina D1 + sIgM/IgD+ Restrictie k/λ CD10. CD7. foliculara. bcl-6 – Fenotipuri aberante: CD5- .• Limfom de manta – Proliferare limfoida monomorfa cu arhitectura difuza. vag nodulara a zonei de manta sau.

– Etiologie: de novo sau prin progresia CLL/SLL.IgM>IgG>IgA . MZL. CD22. anaplazica (celule mari.CD30 + (varianta anaplazica) . NLPHL – Variante : centroblastica.CD10 (30-60% din cazuri) . asem cel S-R). bizari. imunoblastica.CD19. FL. CD79a +/.ki-67>40%!! .CD5 + (10% din cazuri) .• 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. CD20.bcl-6 + (60-90% din cazuri) . IHC: . cu nuclei pleomorfi.

• Limfom Burkitt – Proliferare cu rata de dedublare f crescuta (mitoze multe!). compusa din celule monomorfe cu translocatie myc – IHC • CD19. CD38 + • Translocatie myc la regiunea IGH . bcl-6. CD20. CD22. CD10.

celule centroblast like precum si imunoblaste. IHC: . cu extensie in zonele interfoliculare – In tes epiteliale.utila in diagn diferential cu MCL .abs CD5 – utila in diagn diferential cu MCL si CLL .! Rareori CD5+ . generand leziuni limfoepiteliale. ciclina D1. CD79a + . CD20.limfom extraganglionar alcatuit din limfocite mici centrocit–like. CD23. evidentiind retele de celule dendritice foliculare aflate in foliculii colonizati.• Limfom MALT = limfom de zona marginala extraganglionar • Mi: .CD5.restrictie de lanturi usoare κ/λ (prin care se face diagnosticul diferential cu infiltrate limfoide benigne) . . celulele infiltreaza epiteliul.abs CD10 – utila in diagn diferential cu FCL .abs ciclinei D1.IgM. CD10.CD21 si CD35 +.

CD8+ • CD30.• Limfom cu celule T periferice NOS – IHC: • CD5. CD15 + exceptional • Rearanjare TCR prezenta Limfom anaplazic cu celule mari ALK pozitiv IHC: .ALK+ (de preferat mAb) . CD4. CD7.CD30 + (marcaj membranar si golgian) .

cCD79a. cCD22.• Limfom limfoblastic – neoplazie constituita din celule precursoare (limfoblaste) cu citoplasma redusa si cromatina laxa sau condensata – IHC • CD19. CD10+ • Pax+ • Tdt + .

vimentina. actina. fibrosarcom) – – Contin fibroblaste.Tumori tesuturi moi • T fibroase (fibromatoza. desmin (in masura mai mica). colagen . miofibroblaste si matrice extracelulara (colagen si subst fundam) – IHC.

– Datorita lipsei markerilor specifici pentru acest lineaj. desmina. feritina. CD68. neurofibromas – S100). – Poate fi identificata imunoreactivitate pentru : • Vimentina. diagnosticul se bazeaza pe lipsa markerilor pentru alte lineaje ( DFSP – CD34+++. antitripsina • Focal: Keratine.• T fibrohistiocitare – Derivate probabil din fibroblaste. NF (HFM angiomatoid exp desmina in 50% din cazuri!) Dgn de HFM este mentinut doar in 50% din cazuri .

desi el este indicat in diagn. dif cu HFM – Poate exista expresie focala de actina .• T adipoase – Adipocitele normale si lipoblastele exprima S-100. – T. slab diferentiate pot sa nu exprime deloc acest marker.

glomica • Negativa in t. Leu-7 si chiar CD34 )pot fi prezenti inconstant – atentie la interpretare .• T. de muschi neted – SMA+ (mai sensibila) – Desmina+ – Vimentina + – Caldesmona: • pozitiva in leiomiom. leiomiosarcom.desmoide – ! Alti markeri (CK cu GM mica. t. rabdoide. t. S100.

• T. proteină S100 (in t. muschi striat: • • • • • • • Desmină Actină sarcomerică Miogenină (MyoD1) Miozină Mioglobină Vimentină Focal exprimă: CK. slab diferentiate) şi proteină asociată neurofilamentelor • Ki-67 – factor important .

Des. CD99  Negativ: Des.• Sarcom Ewing extrascheletal  Pozitiv: Vim. NF. Act. NSE  Negativă: CK. ChrA • Tumoră primitivă neuroectodermică  Pozitivă: CD99. Mio. Syn . EMA. Act. GFAP. LCA. Syn  Negativă: markeri musculari • Condrosarcom mezenchimal  Pozitivă: CD99. S100.

• Tumori ale tecii nervului: – Neurofibromul: • Proliferare combinată de elemente ale nervului periferic • IHC – – – – – NSE + axoni S100 + Schwann Vim + fibroblaste EMA + celule perineuriale CD34 + celule ? .

colagen IV.• Schwannomul – Încapsulată – IHC: S100. rar CD68 şi GFAP – Tip A • Celule fusiforme • Palisadă • Corpi Verocay S100 – Tip B • Arii edematoase • Spaţii chistice Schwannom celular . laminină. vim.

CD57 (50%). sarcom sinovial (S100. CK7/19– Diferenţial: leiomiosarcom (S100).CK +/-. CK7/19). pan. melanom cu celule duziforme .• Tumora maligna a tecii nervului periferic: – Pozitiv: S100 (50-70%). proteina bazică a mielinei – EMA negativ.

FVIIIrAg Limfangiomiomul: Act.• T. HMB45 . vasculare – Hemangioendoteliomul : • Keratine. Des. vim. + • CD34+/Angiosarcomul: CD31+ Limfangiom: CD31. CD31. CD34.

PSA are rol in diagnosticul tumorilor slab diferentiate dezvoltate in regiunea cervico-prostatica precum si in diagnosticul tumorilor metastatice (! Poate fi neg dupa hormonoterapie). CK 5/6 . elimina diagn de leziune maligna in leziuni precum atrofia si adenoza ! In prezent se face dublu marcaj p63-AMACR (p504S). .Markeri ai celulelor bazale.• Prostata – AMACR (p504S) • Marker pozitiv al celulelor neoplazice si preneoplazice (PIN) – util in diagn P63. CK 34βE12 (CK903).

CK- .T genitale masculine • Tumori cu celule germinale • Seminomul: – IHC: • PLAP+ (pozitivitate membranara in 90% din cazuri) • C-kit (CD117)+ • CD30. AFP.

18.19+ PLAP + focal (membranar si/sau citoplasmatic) AFPCD117- .• Carcinomul embrionar: – IHC: • • • • • CD30+ CK AE1/AE3. CK4.17.

puternica) CD117 + in aprox 80% din cazuri CD30 - .• T de sac yolk – IHC: • • • • AFP+ CK+ (pozitivitate constanta.

CD99. calretinina + • vimentina + • CK .• T de cordoane sexuale: – IHC: • Inhibina.sau cu pozitivitate variabila .

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