CD45 - leukocyte common antigen
CD3 - T -lymphocyte
CD20(L26) - B lymphocyte
cytokeratin - epithelium
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CD45 is a membrane protein tyrosine phosphatase found on all leukocytes in a number of isoforms. Antibodies such as 2B11 recognize epitopes common to all isoforms and are known as anti-leukocyte common antigen(LCA).
- mark almost all circulating and fixed white cells
- useful in identifying most lymphomas, except roughly 30 % of ALCL and most Hodgkin's disease
CD3: the T-cell antigen receptor binds to the CD3 protein complex at the cell membrane
- A commercially available anti-CD3 antibody is polyclonal and reacts with most T-cell lymphomas in fixed tissue
- exeption being some anaplastic large cell lymphomas and NK leukemia-lymphomas
- very specific, sensitive to T-cell derivation
CD20 epitope is acquired late in the pre-B cell stage of maturation and remains on cells throughout most of their differentiation, although it is lost at the plasma cell stage.
CD20 is strongly positive on
- approximately half of lymphoblastic lymphoma-leukemias
- almost all mature B-cell lymphomas (except plasma cell lesions)
- Reed-Sternberg cells in roughly one quarter of the cases of classic Hodgkin's disease
- almost no T-cell lymphomas
Cytokeratins
The soft epithelial keratin intermediate filaments comprise 1-20 of 30 keratin polypeptides
- Type I (acidic): 9 - 20
- Type II (basic): 1 - 8
- smaller # for each group being the highest molecular weight
- simple vs. complex cytokeratins
Key Dx Points for CK7
- Strongly diffusely positive in most lung, breast, ovarian, endometrial, bladder, thymic, parotid, pancreatic and neuroendocrine carcinomas and mesotheliomas, as well as infibrolamellar hepatoma
- mostly negative - perhaps rare positive cells in colorectal and other GI carcinomas, hepatoma, prostate and renal clel carcinomas, sqamous and small cell carcinomas
- decorate subsets of endothelial cells in normal tissues
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Lymphomas
1) Hodgkin's
- presence of Reed-Sternberg cells (RS cells are CD30+ and CD15+ B-cell origin)
- localized, single group of nodes; extranodal rare; contiguous spread
- Constitutional ("B") signs/symptoms - low-grade fever, night sweats, weight loss
- Mediastinal lymphadenopathy
- 50 % of cases associated with EBV; biomdal distribution - young and old; more common in men except for nodular sclerosing type
- Good prognosis = more lymphocyte, less RS cells
Types: nodular sclerosing, mixed cellularity, lymphocyte predominant, lymphocyte depleted
2) Non-Hodgkin's
- associated with HIV and immunosuppression
- Multiple, peripheral nodes; extranodal involvement common; noncontiguous spread
- majority involve B cells (except those of lymphoblastic T-cell origin)
- No hypergammaglobulinemia
- fewer constitutional signs/symptoms
- peak incidence 20-40 yrs old
Types: small lymphocytic lymphoma, follicular lymphoma, diffuse large cell, mantle cell lymphoma, lymphoblastic lymphoma, Burkitt's lymphoma
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EBV(Epstein-Barr Virus) can cause
[edit] Infectious mononucleosis
Epstein-Barr can cause infectious mononucleosis, also known as 'glandular fever', 'Mono' and 'Pfeiffer's disease'. Infectious mononucleosis is caused when a person is first exposed to the virus during or after adolescence. It is therefore predominantly found in the developed world, as most children in the developing world are found to be already infected by around 18 months of age. EBV antibody tests turn up almost universally positive in developing nations, but only 70-80% positive in the United States[citations needed].
[edit] EBV-associated malignancies
The strongest evidence linking EBV and cancer formation is found in Burkitt's lymphoma and Nasopharyngeal carcinoma. It has been postulated to be a trigger for a subset of Chronic Fatigue Syndrome patients[8] as well as Multiple Sclerosis and other autoimmune diseases.[9]
Burkitt's lymphoma is a type of Non-Hodgkin's lymphoma [1] and is most common in equatorial Africa and is co-existent with the presence of malaria. Malaria infection causes reduced immune surveillance of EBV immortalised B cells, so allowing their proliferation. This proliferation increases the chance of a mutation to occur. Repeated mutations can lead to the B cells escaping the body's cell-cycle control, so allowing the cells to proliferate unchecked, resulting in the formation of Burkitt's lymphoma. Burkitt's lymphoma commonly affects the jaw bone, forming a huge tumour mass. It responds quickly to chemotherapy treatment, namely cyclophosphamide, but recurrence is common.
Other B cell lymphomas arise in immunocompromised patients such as those with AIDS or who have undergone organ transplantation with associated immunosuppression (Post-Transplant Lymphoproliferative Disorder (PTLPD)). Smooth muscle tumors are also associated with the virus in malignent patients.
Nasopharyngeal carcinoma is a cancer found in the upper respiratory tract, most commonly in the nasopharynx, and is linked to the EBV virus. It is found predominantly in Southern China and Africa, due to both genetic and environmental factors. It is much more common in people of Chinese ancestry (genetic), but is also linked to the Chinese diet of a high amount of smoked fish, which contain nitrosamines, well known carcinogens (environmental). alaina wuz hereee
[edit] Chronic fatigue syndrome
In the late 1980s and early 1990s, EBV became the favored explanation for chronic fatigue syndrome. It was noted that people with chronic exhaustion had EBV, although it was also noted EBV was present in almost everyone. In a four year study, the Centers for Disease Control and Prevention found no definitive association between CFS and EBV but it is still being studied by researchers.
Lymphoid associated epithelium
lymphoid epithelial carcinoma
non-keratinizing poorly differentiated squamous cell carcinoma
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mesothelioma causing pleural effusion
TTF-1 to determine tumor lung or thyroid
TTF-1(thyroid transcription factor-1), a nuclear tissue-specific protein transcription factor is found only in thyroid and thyroid tumors regardless of histologic type, as well as in lung carcinomas including
- adenocarcinomas (75%)
- non-small cell carcinomas (63%)
- neuroendocrine and small cell carcinomas (>90%)
- squamous cell carcinomas (10%)
selectively expressed during embryogenesis in the thyroid, the diencephalon of the brain and in respiratory epithelium, TTF-1 binds to and activates factors for surfactant protein derived from Clara cells
TTF-1 rarely seen in carcinomas outside the lung or thyroid
