How to differentiate? Grayzone lymphoma (Grayzonelymphoma) is a new type of lymphoma proposed by the WHO classification in 2017 [2,3], which first had an indistinguishable type between Burkitt lymphoma and diffuse large B lymphoma, and an indistinguishable type between classical Hodgkin’s lymph and diffuse large B lymphoma. The former has now been abolished in academia, and only the latter has been retained. This is because a Burkitt lymphoma can be classified as Burkitt lymphoma if it has an atypical morphology with immunohistochemistry and characteristics of Burkitt lymphoma, such as BCL-2 positivity; a striking lymphoma if FISH has C-MYC, BCL2 and or BCL6 positivity; and a lymphoma with a morphology intermediate between diffuse large B and absent Burkitt lymphoma without C-MYC, BCL2 and or BCL6 positive, the diagnosis is high-grade B-cell lymphoma, non-specific (NOS). Currently, the only “indistinguishable type between classical Hodgkin’s lymphoma and diffuse large B lymphoma” is gray zone lymphoma, whose immunophenotype is often positive for CD45, often positive for CD15, CD20, CD30, and CD79a, often negative for CD10 and ALK, and often positive for B-cell transcription factors such as PAX5, BOB.1, and OCT-2. OCT-2 are often positive, and EBV is often positive. If the morphology is more like primary mediastinal large B-cell lymphoma, if weakly or not expressing CD20, strongly expressing CD30, CD15, it is basically a gray zone lymphoma, if the morphology is more like classic Hodgkin’s lymphoma, if strongly expressing CD20, and or other B-cell markers (e.g. CD19, CD20, CD22, CD79a), not expressing CD15, it is basically a gray zone lymphoma. Classical Hodgkin (cHL) is often CD15,CD30,ebv positive (~40%), but immunophenotyping is often helpful to distinguish it from PMBL, CD15 (85% expression), high CD30 expression (>99% expression), lack of all-B (e.g. CD19,CD20,CD22,CD79a) and all-T antigens (e.g. CD3,4,5,8 less than 10, etc.) . Primary mediastinal large B-cell lymphoma (PMBL) and classical Hodgkin are often indistinguishable, both have RS cells and both have PD1 expression. However, the immunophenotype is often distinguishable from cHL, expressing all-B (e.g. CD19, CD20, CD22, CD79a), often MAL-1 and CD200, CD45, CD30 (weak), TRAF-1, nuclear c-REL, rarely CD15, and specifically not immunoglobulins, CD5 and CD10. PMBL only invades the mediastinum, while DLBCL is also present outside the nodes. (The threshold for C-MYC, BCL-2, and BCL-6 immunohistochemistry is generally 40%). Clinical staging of lymphoma is mainly of interest to good clinicians, and pathology is relatively unconcerned mainly because there is no incentive or reward to study new staging and publish articles, because it has been done long ago abroad, and it does not enter the title and suffers in vain, and there is no penalty for sending wrong reports anyway. And clinicians care, can change the treatment plan, patients get a better prognosis, that kind of happiness is the original intention as a doctor, is how much money can not buy. Useful? Gray area lymphoma treatment R-CHOP effect is not good, DA-EPOCH effect is good, expected other R-CHOP + X or clear marrow treatment effect is also good, because this disease is relatively new, better to publish articles. PMBL although NCCN guidelines recommend 6 courses of R-CHOP + – radiotherapy, but uptodate recommends that must be combined with radiotherapy, or with DA-EPOCH, pure R-CHOP effect is not good. Whether radiotherapy is given or not determines whether the woman has a requirement for breastfeeding or breast protection. For diffuse large B-cell lymphoma, R-CHOP therapy is sufficient if it is a germinal center type. If it is a non-germinal center type, uptodate is still recommended for clinical trials such as R-CHOP + X. X can be BTK (not available for patients over 60 years old), lenalidomide, pontizomib, hyperCVAD, or others. In conclusion, different types of disease with different prognosis and different treatment options are used. Prognosis-related molecular markers are yet to be discovered, probably like in sleeve cell lymphoma, where TP53 positivity may be a risk indicator of poor prognosis in DLBCL.