Original Article

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Blood Res 2020; 55(4):

Published online December 31, 2020

https://doi.org/10.5045/br.2020.2020070

© The Korean Society of Hematology

First report of the unique expression of RECAF (receptor for alfa feto-protein) in adult B-NHL/CLL patients

Hebatallah Adel Sedky1, Soha Raouf Youssef1, Doaa Ahmad Gamal1, Heba Fawzy Houssein1, Walaa Ali Elsalakawy2

1Clinical Pathology Department, 2Clinical Hematology and Bone Marrow Transplant Unit, Internal Medicine Department, Ain Shams University, Faculty of Medicine, Cairo, Egypt

Correspondence to : Walaa Ali Elsalakawy, M.D.
Clinical Hematology and Bone Marrow Transplant Unit, Internal Medicine Department, Ain Shams University, Faculty of Medicine, Cairo 11241, Egypt
E-mail: drwalaa2010@gmail.com

Received: April 7, 2020; Revised: October 3, 2020; Accepted: November 12, 2020

Abstract

Background
Lymphoproliferative disorders (LPDs) are a heterogeneous group of diseases characterized by an uncontrolled production of monoclonal lymphocytes. RECAF is the receptor for alpha-fetoprotein, which is re-expressed on malignant cells, thus serving as a broad-spectrum tumor marker.
Methods
The current study is a retrospective study carried out on 200 archival bone marrow trephine biopsy specimens [60 normal control (NC), 38 pathological control (PC) and 102 lymphoproliferative diseases (LPD) specimens]. RECAF expression was assessed using immunohistochemistry.
Results
The percentage of cells that are positive for RECAF was significantly higher in the LPD group than in the NC group (P=0.007), while there was no significant difference between non-Hodgkin lymphoma (NHL) patients and PC regarding the number of RECAF positive cells (P=0.1). RECAF showed a unique expression pattern among the different subtypes of LPD. None of the hairy cell leukemia (HCL) expressed RECAF, while the highest percentage was seen in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) (P=0.001). Compared to routine histopathology, RECAF was more sensitive in detecting bone marrow (BM) infiltration in FL, mantle cell lymphoma (MCL), and DLBCL (P=0.01).
Conclusion
RECAF is significantly expressed in the BM of NHL/chronic lymphocytic leukemia (CLL) patients. RECAF shows a unique expression pattern among the different subtypes of LPD. Furthermore, RECAF may help to detect bone marrow infiltration in lymphoma cells. This may help in the diagnosis, follow-up, and targeting of LPD.

Keywords Lymphoma, RECAF, Hairy cell leukemia, Chronic lymphocytic leukemia, Diffuse large B cell lymphoma, Follicular lymphoma

Article

Original Article

Blood Res 2020; 55(4): 253-261

Published online December 31, 2020 https://doi.org/10.5045/br.2020.2020070

Copyright © The Korean Society of Hematology.

First report of the unique expression of RECAF (receptor for alfa feto-protein) in adult B-NHL/CLL patients

Hebatallah Adel Sedky1, Soha Raouf Youssef1, Doaa Ahmad Gamal1, Heba Fawzy Houssein1, Walaa Ali Elsalakawy2

1Clinical Pathology Department, 2Clinical Hematology and Bone Marrow Transplant Unit, Internal Medicine Department, Ain Shams University, Faculty of Medicine, Cairo, Egypt

Correspondence to:Walaa Ali Elsalakawy, M.D.
Clinical Hematology and Bone Marrow Transplant Unit, Internal Medicine Department, Ain Shams University, Faculty of Medicine, Cairo 11241, Egypt
E-mail: drwalaa2010@gmail.com

Received: April 7, 2020; Revised: October 3, 2020; Accepted: November 12, 2020

Abstract

Background
Lymphoproliferative disorders (LPDs) are a heterogeneous group of diseases characterized by an uncontrolled production of monoclonal lymphocytes. RECAF is the receptor for alpha-fetoprotein, which is re-expressed on malignant cells, thus serving as a broad-spectrum tumor marker.
Methods
The current study is a retrospective study carried out on 200 archival bone marrow trephine biopsy specimens [60 normal control (NC), 38 pathological control (PC) and 102 lymphoproliferative diseases (LPD) specimens]. RECAF expression was assessed using immunohistochemistry.
Results
The percentage of cells that are positive for RECAF was significantly higher in the LPD group than in the NC group (P=0.007), while there was no significant difference between non-Hodgkin lymphoma (NHL) patients and PC regarding the number of RECAF positive cells (P=0.1). RECAF showed a unique expression pattern among the different subtypes of LPD. None of the hairy cell leukemia (HCL) expressed RECAF, while the highest percentage was seen in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) (P=0.001). Compared to routine histopathology, RECAF was more sensitive in detecting bone marrow (BM) infiltration in FL, mantle cell lymphoma (MCL), and DLBCL (P=0.01).
Conclusion
RECAF is significantly expressed in the BM of NHL/chronic lymphocytic leukemia (CLL) patients. RECAF shows a unique expression pattern among the different subtypes of LPD. Furthermore, RECAF may help to detect bone marrow infiltration in lymphoma cells. This may help in the diagnosis, follow-up, and targeting of LPD.

Keywords: Lymphoma, RECAF, Hairy cell leukemia, Chronic lymphocytic leukemia, Diffuse large B cell lymphoma, Follicular lymphoma

Fig 1.

Figure 1.Diffuse RECAF positive reaction in the majority of cells in DLBCL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 2.

Figure 2.Diffuse RECAF positivity in DLBCL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 3.

Figure 3.Collections of RECAF-positive cells in DLBCL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 4.

Figure 4.Sporadic RECAF-positive cells in DLBCL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 5.

Figure 5.Many and deeply stained RECAF-positive cells in DLBCL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 6.

Figure 6.RECAF-positive follicle (on the left) and a negative follicle (right) in the FL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 7.

Figure 7.A collection of RECAF-positive cells surrounded by negative cells in FL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 8.

Figure 8.Diffuse RECAF positivity in FL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 9.

Figure 9.Many and deeply stained RECAF-positive cells in MCL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 10.

Figure 10.Many and deeply stained RECAF-positive cells in MCL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 11.

Figure 11.Scattered RECAF-positive cells in CLL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 12.

Figure 12.HCL negative for RECAF.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 13.

Figure 13.HCL negative for RECAF.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 14.

Figure 14.Sporadic RECAF-positive cells in neuroblastoma.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 15.

Figure 15.Collections of RECAF-positive cells in ALL.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 16.

Figure 16.Few RECAF-positive cells in Multiple Myeloma.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 17.

Figure 17.Sporadic RECAF-positive cells in neuroblastoma.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 18.

Figure 18.Placental tissue stained with RECAF (positive control).
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Fig 19.

Figure 19.Normal control negative for RECAF.
Blood Research 2020; 55: 253-261https://doi.org/10.5045/br.2020.2020070

Table 1 . Descriptive data of studied groups..

ParameterNCPCNHL
Age, yr (mean±SD)37±7.824.2±7.348±11.2
Gender, male/female32/2821/1747/55
Hb, g/dL (mean±SD)11.5±1.411.5±2.211.9±1.1
Platelets, cells×103/mL (mean±SD)217±51.3216.8±68.8271.1±86.8
LDH, mg/dL (mean±SD)292±37.7336±70.6540.4±176.7
Lymphocytes, cells× 103/mL (median and IQ range)1.8 (2.2)1.9 (23.3)2.4 (16.7)

Abbreviations: Hb, hemoglobin; HSM, hepatosplenomegaly; LDH, lactate dehydrogenase; LNS, lymph nodes; NC, normal control; NHL, non-hodjken lymphoma; PC, pathological control; SD, standard deviation..


Table 2 . Descriptive data of NHL/CLL cases subgroups included in the study..

ParameterDLBCL (N=44)FL (N=22)MCL (N=10)CLL (N=14)HCL (N=12)
Age, yr (mean±SD)43.5±10.850.6±11.548±4.355±8.852±14.2
Gender (male/female)26/188/148/26/86/6
Hb, g/dL (mean±SD)12.1±1.211.8±0.911.8±0.811.6±0.310.2±1.4
Platelets, cells×103/mL(mean±SD)313±76.6245.8±73.8225.6±51.7159.2±9.9106.5±20.3
LDH, mg/dL (mean±SD)555.3±159.6613.8±148.1730±105.1434.7±146.9316.3±44.4
Lymphocyte count, cells×103/mL (median and IQ range)2.2 (2.5)2 (2.4)2.6 (2.4)19 (22)2.2(2.5)
B-symptoms, N (%)18 (40.9)8 (36.4)2 (20)4 (28.6)8 (66.7)
LNS, N (%)44 (100)22 (100)10 (100)10 (71.4)2(16.7)
HSM, N (%)20 (45.5)10 (45.5)2 (20)8 (57.1)10 (83.3)
Stage, N (%)
Stage18 (18.2)2 (9.1)0 (0)0 (0)0 (0)
Stage 214 (31.8)2 (9.1)0 (0)0 (0)0 (0)
Stage 36 (13.6)4 (18.2)4 (40)0 (0)0 (0)
Stage 416 (36.4)14 (63.6)6 (60)14 (100)12 (100)
BM infiltration by histopathology, N (%)12 (27.3)12 (54.5)2 (20)14 (100)12 (100)

Abbreviations: Hb, hemoglobin; HSM, hepatosplenomegaly; LDH, lactate dehydrogenase; LNS, lymph nodes; N, number; SD, standard deviation..


Table 3 . Comparison between different B-NHL subgroups as regards percent of RECAF positive cases..

ParameterDLBCLFLMCLCLLHCL
RECAF+ve cases, N (%)16/44 (36.1)20/22 (90.9)8/10 (80)6/14 (42.8)0 (0)
Fisher exact testP<0.001

Table 4 . Comparison between RECAF negative and RECAF positive NHL cases as regards laboratory findings..

RECAF (cutoff)

NegativePositiveT-test



Mean±SDMean±SDtP
Lymphocyt6.000±8.5324.100±5.4590.9720.336
HB12.050±1.25511.803±1.0680.7520.456
Platelet273.650±91.468269.516±85.2810.1640.870
LDH597.000±143.546503.903±188.3751.8830.066
Age47.900±10.95948.194±11.626-0.0900.929

Abbreviations: Hb, hemoglobin; LDH, lactate dehydrogenase; SD, standard deviation..


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