Atypical lymphoplasmacytic and immunoblastic proliferation: A Systematic Review

Abstract

Atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) was first reported in 1984 as characteristic histological findings in lymph nodes associated with autoimmune diseases, but it has not been clearly defined to date. To summarize the histological characteristics and clinical diagnoses associated with ALPIBP, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "atypical lymphoplasmacytic and immunoblastic lymphadenopathy" from their inception to December 27, 2023. We also summarized the courses of three cases with a pathological diagnosis of ALPIBP. Nine articles with 52 cases were included. Among the total of 55 cases, including the three from our institution, the median age of the cases was 63.5 years with a female predominance (69.5%). Lymphadenopathy was generalized in 65.6% and regional in 34.4% of cases. RA (24.4%), SLE (24.4%), and autoimmune hemolytic anemia (20.0%), were common clinical diagnoses. A combination of cytotoxic chemotherapy was used in 15.6% of cases due to the suspicion of malignancy. Nodal T-follicular helper cell lymphoma, angioimmunoblastic type, methotrexate-associated lymphoproliferative disorders, and IgG4-related diseases were listed as important diseases that need to be pathologically differentiated from ALPIBP. This review summarizes the current understanding of the characteristics of ALPIBP. Given that underrecognition of ALPIBP could lead to overdiagnosis of hematological malignancy and unnecessary treatment, increased awareness of the condition in pathologists and clinicians is crucial.

Keywords: IgG4-related disease; angioimmunoblastic T-cell lymphoma; atypical lymphoplasmacytic and immunoblastic proliferation; systematic review.

Fig. 1

PRISMA flowchart of the search strategy

Fig. 2

Histopathological features of ALPIBP (Case 1: H&E staining) a, b: The follicular structure is obscured and the interfollicular area is expanded. c: Vascular proliferation with plump endothelial cells is seen in the expanded interfollicular area. d: Immunoblasts with large nuclei and distinct nucleoli (arrow heads) are observed with a background of small lymphocytes and plasma cells. e: Mitotic figures (arrow heads) are easily observed.

Fig. 3

Immunohistochemical findings of ALPIBP (Case 1) a (H&E): Immunoblasts with a distinct nucleolus. b (CD20 staining), c (CD30 staining), d (CD15 staining): Immunoblasts typically exhibit CD20 positivity, with occasional CD30 positivity. They are negative for CD15. e (IgG4 staining), f (IgG staining): While there is an increased number of IgG4-positive cells, the IgG4/IgG-positive cell ratio remains below 40%. g (IL-6 staining): IL-6 staining was weakly positive for follicular B cells and widely positive for interfollicular plasma cells.