CD4-positive diffuse large B-cell lymphoma: A variant with aggressive clinical potential

Table 1 Summary of histologic and clinical features of ALK-negative, CD4-positive diffuse large B-cell lymphomas

Case no.	Age/sex	Diagnosis	Immunophenotype	Molecular findings	Gross description	Treatment	Clinical outcome	Site	Stage
1	73/M	DLBCL	CD20, BCL-2, CD10, CD5, CD43, BCL-6, and CD4		Soft, gelatinous appearing mass	R-CHOP × 4	Complete remission at 4 mo follow-up; free of disease at 6 mo follow-up	Left maxillary sinus	I-E
2	22/F	PMLBCL	CD45, CD20, CD79a, with variable expression of CD2, CD4, CD30, CD23, BCL-6 and BCL-2			12 cycles of R-VACOP-B; 2 cycles of R-ESHAP mediastinal radiation (40-50 Gy); matched, unrelated donor stem cell transplant with Bu/Cy conditioning; salvage chemotherapy with GND; SGN-35	Dead; 14 mo survival from disease discovery; Progressive disease	Supraclavicular lymph node	IIE-X-B
3	79/F	DLBCL and FL(3a)	CD45 (focal), CD20, CD3, CD21 (focal), Bcl-2, Pax-5, subset expression of CD2, CD4, CD5, CD7, CD8 Bcl-6, MUM1, and CD10			R-CHOP	Dead; 6 mo survival from disease diagnosis	Left neck lymph node
4	67/M	CLL/SLL with transformation to LBCL	CD45, CD30, EMA, CD4 (subset), and CD43, rare weak CD2	46, XY[18]; clonal IGH rearranged; IGVH unmutated; TCR gamma rearrangement negative		Fludarabine and cytoxan × 3; fludarabine, Rituxan, and mitoxantrone × 2; R-CHOP × 4; R-CHOP; BEAM and auto transplant	Dead; 15 mo survival; Progressive disease	Left subclavicular lymph node
5	26/M	B-cell large cell lymphoma	CD20, CD30 (weak), CD4 (subset)			R-CHOP × 5, field radiotherapy	No evidence of relapse at 72 mo; lost to follow up	Left posterior cervical lymph node	IV-A-E
6	55/F	Malignant lymphoma, diffuse cleaved large cell type, with B-cell differentiation	CD20, MB-2, CD4, BCL2, and CD43 PCNA				Lost to follow-up	Right leg skin

CLL/SLL: Chronic lymphocytic leukemia/small lymphocytic lymphoma; CD: Cluster of differentiation; DLBCL: Diffuse large B-cell lymphoma; F: Female; M: Male; PMLBCL: Primary mediastinal large B-cell lymphoma; CHOP: Rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate; R-ESHAP: Rituximab, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin; VACOP: Vinblastine, adriamycin, cyclophosphamide, etoposide, prednisone, bleomycin; GND: Gemcitabine, vinorelbine, and doxorubicin; SGN-35: Brentuximab vedotin; BEAM: Carmustine, etoposide, cytarabine, and melphalan; FL: Follicular lymphoma.

Table 2 Summary of ALK-negative, CD4-positive diffuse large B-cell lymphomas reported in the literature

Case no.	Age/sex	Diagnosis	Immunophenotype	Molecular findings	Gross description	Treatment	Clinical outcome	Site	Stage	Ref.
1	81/F	DLBCL	CD19, CD4, CD7				Lost to follow-up after 13 mo of stable disease	N/A	III	[2]
2	82/M	DLBCL	CD4+, CD5+, CD19+, CD20+, CD23+, CD25+, kappa+			R-CHOP × 5	Complete remission after chemotherapy	Left cervical and left inguinal lymph node		[11]
3	55/F	DLBCL	CD20 (weak), BCL2, PAX5, surface kappa, MUM1, and CD4	Clonal IgH gene rearrangement and no BCL2 gene rearrangement	Uniformly soft, greyish tissue	Mega Chop; R- Mega CHOP × 5	Complete remission after chemotherapy	Ileum		[6]
4	73/M	DLBCL	CD45 (dim), CD19, PAX5, CD20, CD10, BCL6, BCL2, surface lambda light chain, and CD4	Clonal IgH gene rearrangement and a BCL2 gene rearrangement		Adjuvant chemotherapy		Ileum		[6]

CD: Cluster of differentiation; DLBCL: Diffuse large B-cell lymphoma; F: Female; M: Male; N/A: Not available; CHOP: Rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, mega.