الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 128 |  |  |
| | | from | 128 | | |
Abstract
Hodgkin lymphoma is one of the neoplasms that show a very promising prognosis if it is early and accurately diagnosed. Despite being an uncommon neoplasm but it still represents an economic burden by increasing morbidity of the patients. It roughly represents 15% of all cancers in young adults, and 8.4% of the new cancer cases per year in the Egyptian population.
Histologic subtype of Hodgkin lymphoma directly influences the prognosis and therapy of this neoplasm, as NLPHL runs more indolent course than CHL, yet more frequently relapses. However it has good response to therapy, so overall prognosis is better than CHL. Also, the therapeutic regimens completely totally differ in both subtypes. Thus, differentiating the two main subtypes of Hodgkin lymphoma - NLPHL and CHL - will improve the outcome of the cases.
Diagnosis and subtyping of Hodgkin lymphoma in most of the cases isn’t clear by routine H&E staining alone, and it requires additional IHC staining. So, further investigation of immunostaining markers is done to reach the appropriate panel that will help in diagnosis and subtyping. Among those well-established markers are CD15, CD30, CD20 and CD3. Positivity for CD15 & 30 with negativity to CD20 in HRS cells, together with positivity to both CD20 and CD3 in the reactive background with prevalence of CD3 confirms the diagnosis of CHL. Positivity for CD20 with negative CD15 & CD30 in LP cells with positivity to both CD20 and CD3 in the reactive background confirms the diagnosis of NLPHL. However, still some cases of NLPHL and CHL show overlapping immune staining results. This necessities further studies to detect other useful markers in differentiating these types.
GATA3 immune marker is a recently described transcription marker expressed by breast epithelium, urothelium, as well as a subset of T-lymphocytes. Depending on the last site mentioned, GATA3 expression has been investigated in lymphomas in various studies, yet in this research, it is investigated in HL.
CD79a is an immune marker for B-cells which is used to differentiate T cell lymphomas from B cell lymphomas especially in the anaplastic lymphomas.
The present work aimed at investigating the validity of both GATA3 and CD79a expression in Hodgkin lymphoma subtypes. It also aimed at investigating the possible use of GATA3 in differentiating NLPHL from CHL.
The present work has been carried on seventy cases of HL and three CHL cases not fulfilling the immune criteria of CHL. All cases were collected retrospectively from the archive of the pathology department, MRI, Alexandria University and the archive of other private pathology laboratories during the period from April 2019 to April 2020.
Seventy HL cases were subdivided according to availability into: NLPHL and CHL further subdivided into; NS, MC, LR and LD. However the other three cases were
classified as CHL cases with overlapping immune pattern and so, were excluded from the statistical analysis.
Serial of 5μm thick paraffin sections from all obtained blocks have been subjected to:
1) Routine H&E stain: to review the pathology and ensure adequacy of the specimen.
2) Review &/or re-stain CD15, CD30, CD20 and CD3.
3) GATA3immune staining.
4) CD79a immune staining.
The expression of GATA3 was detected as brown colouration in the nuclei of the large neoplastic cells. Positivity in the nuclei of the small cells wasn’t counted as positive. Scoring was strong when >30% of the neoplastic cells were positive, moderate when <30% of the neoplastic cells were positive and negative when all the neoplastic cells were completely negative.
Expression of CD79a was detected as brown colouration in the cytoplasm of the large neoplastic cells. Again any staining in other cells wasn’t counted. Scoring was either positive or negative.
Results showed that GATA3 expression was mainly in CHL as forty-nine out of the sixty CHL cases were positive for GATA3 while all the included cases of NLPHL were negative for GATA3. These results state that the specificity of GATA3 in differentiating CHL from NLPHL is 100%. Its positive predictive value is 100 as the probability to detect CHL was forty-nine cases against none among NLPHL cases.
All the cases of NLPHL were positive for CD79a while only seven cases out of the included sixty CHL cases showed positivity to CD79a. These results proved that the sensitivity of CD79a in differentiating NLPHL from CHL is 100%. Its negative predictive value is 100 as its probability to exclude NLPHL was 100%.
In conclusion, GATA3 nuclear expression is a good confirmatory test for CHL, yet not a good negative, as its negativity doesn’t exclude CHL. GATA3 coupled with CD79a is a good test to diagnose NLPHL.
Two out of the three included cases of CHL with unusual immune results showed moderate positivity for GATA3 marker. The three cases were positive for CD79a, thus typifying these cases as grey zone lymphoma cases.
GATA3 could possibly be used in cases suspected to be HL as a second line after CD15 as it may help diagnosing HL cases that may be negative for CD15. This is because two of the CHL cases expressed GATA3 despite being completely negative for CD15.
Not only playing role in diagnosis but also GATA3 could play role in therapeutic strategies due to recent application of targeted therapy towards this transcription factor in other diseases as asthma.
Finally, immune staining alone can never reach the diagnosis without being coupled with the routine H&E results. Yet, immune staining still takes the upper hand in diagnosing HL above flow cytometry and conventional PCR due to few neoplastic cells in relation to abundant reactive inflammatory background cells that results in false negative results.