The significance of 18F-FDG PET/CT in secondary hemophagocytic lymphohistiocytosis.

This study was aimed to investigate the significance of 18F-FDG PET/CT in secondary hemophagocytic lymphohistiocytosis (sHLH) patients. A total of 18 patients received 18F-FDG PET/CT scan at initial diagnosis. All patients (18/18) had at least 3 organs involved, with increased FDG metabolism in different degrees. Fifteen cases (15/18) had definite underlying diseases, including infections (IAHLH), rheumatosis (RAHLH), or malignancy (MAHLH). The SUVmax of patients in MAHLH group was significantly higher than patients in IAHLH group or RAHLH group (P = 0.015, P = 0.045). Furthermore, the SUVmax of patients in IAHLH group was significantly higher than patients of RAHLH group (P = 0.043). Therefore, we concluded that 18F-FDG PET/CT may especially play important role in differential diagnosis of sHLH.

To the Editor

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a hyper-inflammatory clinical syndrome mainly caused by severe infections, autoimmune inflammatory disorders and malignancies, especially lymphoma [1-3]. Up to date, very few data from the literature are available regarding the role of 18F-FDG PET/CT in sHLH. In this study, 18 of 50 patients with sHLH who were admitted into our hospital between May 2007 and December 2010 underwent the examination (Table 1). The male-to-female ratio was 1:1, and the median age was 35 years (15-73). The diagnosis of HLH was made according to HLH-2004 diagnostic guidelines [4,5], and the underlying diseases were confirmed by a series of pathogenesis examinations including pathology, immunology, bacterial culture and virus detection et al. The maximum standardized uptake values (SUVmax) used to measure the level of FDG uptake were determined in all lesions [6]. All of the 18 patients had at least 3 organs involved, with increased FDG uptake at different level, including 18 cases showing splenomegaly, 16 cases serous effusions, 16 cases lymphadenopathy, 13 cases bone lesions, 12 cases pneumonia, 8 cases hepatomegaly, 5 cases brain parenchymal or cerebroventricular lesions, 5 cases cholecystitis, 4 cases myocardium lesions, and 2 cases kidney calculi. There were also other organs involved, such as larynx, muscles and adnexauteri. Fifteen patients (15/18) had definite underlying diseases, and were divided into three groups.,including Infection Associated HLH (IAHLH, including EBV-HLH, n = 8), Rheumatosis Associated HLH (RAHLH, n = 2), and Malignancy Associated HLH (MAHLH, n = 5). The SUVmax of patients in MAHLH group was significantly higher than those of patients with IAHLH (Mean 12.0 vs. 6.8, P = 0.015), and RAHLH (Mean 12.0 vs. 2.7, P = 0.045). Furthermore, the SUVmax of patients with IAHLH was significantly higher than that of patients with RAHLH (Mean 6.8 vs. 2.7, P = 0.043). However, no significant difference in survival time was found between the three different sHLH subtype according to Kaplan-Meier analysis (P >0.05). In conclusion, 18F-FDG PET/CT may play important role in differential diagnosis of sHLH, with high SUV pointing toward underlying malignancy.

Table 1

Characteristics of 18 sHLH patients

No.	Age/ Sex	Underlying disease	Therapy	Outcome	Survival (month)	Organs	SUV max
1	35/M	Lymphoma (NK / T)	IVIG/HLH-2004 regimen(1 cycle) → High-dose methylprednisolone pulse therapy	Died of intracranial hemorrhage	1.7	6	12.3
2	35/F	Lymphoma (NK / T)	The Hyper-CVAD regimen (1 cycle)	Died of intracranial hemorrhage	1.2	6	15.7
3	18/M	Lymphoma (NK / T)	The CHOP regimen(1 cycle)	Died of acute hemorrhage of gastrointestinal tract	0.3	7	14.6
4	56/M	Lymphoma	Hydrocortisone 100mg×5d	Died of intracranial hemorrhage	1.7	5	4.3
5	32/M	Lymphoma	Dex 10mg/d×3d	Died of liver failure	0.3	10	13.3
6	37/F	Sjögren's syndrome	The COP regimen(3 cycle)	CR	>12	5	0.7
7	15/F	UCTD	The COP regimen (4 cycle)	CR	>45	3	4.6
8	21/F	EBV infection	HLH-2004 regimen (1 cycle)	Died of acute hemorrhage of gastrointestinal tract	1.7	7	6.6
9	17/M	EBV infection	Methylprednisolone 40 mg/d×24d	CR	>22	7	8.3
10	46/M	EBV infection	Dex 15mg/d×4d	Died of septic shock	0.4	6	10
11	73/M	EBV infection	The COP regimen (7 cycle)	Died of multi-organ failure	6	7	5.2
12	26/F	CMV infection	IVIG/HLH-2004 regimen (1 cycle) →The CHOP regimen(2 cycle)	CR	>24	6	9
13	24/F	CMV infection	The COP regimen (7 cycle)	Died of respiratory failure	2.2	5	4.2
14	69/F	MRSH infection	The COP regimen (2 cycle)	Died of respiratory failure	2.0	6	5.2
15	62/F	Fungal Infection	The COP regimen (7 cycle)	stable	>8	4	5.8
16	44/F	Malignant tumour?	Methylprednisolone 40 mg/d×5d	Died of multi-organ failure	0.4	8	7.7
17	56/M	Lymphoma?	The CHOP regimen (2 cycle) →Splenectomy→The Hyper-CVAD regimen (1cycle)	stable	>13	6	5.7
18	18/M	indefinite	HLH-2004 regimen (1 cycle)	Died of intracranial hemorrhage	0.2	3	4.2

HLH-2004, dexamethasone, etopside and Ciclosporin A; CHOP, cyclophosphamide, adviamycin, vincristine and prednisolone; COP, cyclophosphamide, vincristine and prednisone; Hyper-CVAD, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine; DEX, dexamethasone; CR, complete response; UCTD, undifferentiated connective tissue disease; EBV, Epstein-Barr virus; CMV, cytomegalovirus; MRSH, methicillin-resistant Staphylococcus hominis.