Guillain-Barré syndrome and hemophagocytic syndrome heralding the diagnosis of diffuse large B cell lymphoma: A case report

Table 1 Diagnostic criteria for diffuse large B cell lymphoma, Guillain-Barré syndrome and hemophagocytic syndrome

	Diffuse large B cell lymphoma	Guillain-Barré syndrome[3]	Hemophagocytic syndrome[4]
Diagnostic criteria	Diagnosis is based on WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues	Bilateral and flaccid weakness of limbs Decreased or absent deep tendon reflexes in weak limbs; Monophasic course and time between onset-nadir 12 h to 28 d; CSF cell count < 50/μL1; CSF protein concentration > normal value1; NCS findings consistent with one of the subtypes of GBS; Absence of alternative diagnosis for weakness	The diagnosis HLH can be established if either 1 or 2 below is fulfilled: (1) A molecular diagnosis consistent with HLH; and (2) Diagnostic criteria for HLH fulfilled five out of the eight criteria below. (A) Initial diagnostic criteria (to be evaluated in all patients with HLH); Fever; Splenomegaly; Cytopenias (affecting 2 of 3 lineages in the peripheral blood): Hemoglobin < 90 g/L (in infants < 4 wk: Hemoglobin < 100 g/L). Platelets < 100 × 109/L. Neutrophils < 1.0 × 109/L; Hypertriglyceridemia and/or hypofibrinogenemia: Fasting triglycerides 3.0 mmol/L (i.e., 265 mg/dL); Fibrinogen < 1.5 g/L; Hemophagocytosis in bone marrow or spleen or lymph nodes; No evidence of malignancy. (B) New diagnostic criteria; Low or absent NK-cell activity (according to local laboratory reference); Ferritin 500 mg/L; Soluble CD25 (i.e., soluble IL-2 receptor) 2400 U/mL

¹If colony-stimulating factor is not collected or results not available, nerve electrophysiology results must be consistent with the diagnosis Guillain-Barré syndrome.

NCS: Nerve conduction studies; GBS: Guillain-Barré syndrome; HLH: Hemophagocytic lymphohistiocytosis; CSF: Colony-stimulating factor.

Table 2 Reported cases of diffuse large B cell lymphoma combined with Guillain-Barré syndrome

Case	Publication year	Country	Age (yr)/gender	Type of GBS	Immune performance	Nerve conduction studies	Onset of GBS	Treatment of GBS and lymphoma	Response to treatment with IVIG/plasmapheresis	Ref.
1	2015	Australia	F/72	AMSAN	Negative	Absent sensory and motor responses and decreased amplitude in the upper and lower limbs, absent H reflexes, and reduced F waves in the upper and lower limbs	After chemotherapy	GBS: IVIG, 400 mg/kg/dx 5 d. Lymphoma: R-CHOP, radiotherapy	Progress is fast, dead	[1]
2	2013	Pakistan	M/70	Unknown	Unknown	Undetectable H reflexes, prolonged distal motor latencies in the right tibial, right ulnar, and bilateral median nerves, evidence of a conduction block in the right tibial nerve. Electromyography (EMG) showed no evidence of denervation	Before chemotherapy	GBS: IVIG 1 g/kg. Lymphoma: R-CHOP	Yes, recurrence of GBS, dead	[9]
3	2013	Germany	M/75	Unknown	GM2 IgM	Axonal-demyelinating sensorimotor polyneuropathy was accentuated in the legs and the sensory system	After chemotherapy	GBS: IVIG, 30 g/dx 3 d, plasmapheresis. Lymphoma: R-CHOP	No	[10]
4	2015	China	M/65	Atypical, the exact type is unknown	Unknown	Unknown	Spinal cord compression	Methylprednisolone, 500 mg	Unknown	[11]
5	2012	Japan	F/83	Unknown	Unknown	Unknown	After chemotherapy	GBS: IVIG, steroid pulse (the dosage is unknown). Lymphoma: CHOP, R-CHOP	Yes, CMV infection, dead	[12]
6	2019	Japan	M/67	Unknown	Unknown	Prolonged distal motor latencies in the median and ulnar nerves and decreased motor and sensory nerve conduction velocities in the median, ulnar, and tibial nerves	Before chemotherapy	GBS: IVIG, 400 mg/kg/dx 5 d. Lymphoma: High-dose CTX	No, dead	[13]
7	2020	USA	M/67	Unknown	Negative	Unknown	After chemotherapy	GBS: IVIG, 400 mg/kg/dx 5 d. Lymphoma: R-DA-EPOCH	Yes, Residual neurological deficits present	[14]
8	2019	China	unknown	Unknown	GM1 IgM, GD1b IgM	Absent sensory action potentials in the lower limbs	Unknown	Unknown	Unknown	[15]
9	2012	United States	M/61	Miller Fisher syndrome (MFS)	Negative	Prolonged distal motor latency (right median, ulnar, and tibial motor nerves), slowed motor nerve conduction velocity (right median and tibial motor nerves), prolonged minimum F-wave latencies (right median, ulnar, and tibial nerves), or absent F-waves (left fibular nerve)	Before chemotherapy	GBS: IVIG, 400 mg/kg/dx 5 d. Lymphoma: R-CHOP	Yes, recurrence of GBS, improved after chemotherapy, died of pulmonary embolism	[16]
10	2018	Japan	F/48	GBS-like	Unknown	Unknown	Neurolymphomatosis	GBS: IVIG, steroid pulse (dosage is unknown). Lymphoma: R-CHOP	Yes, recurrence of GBS, dead	[17]
11	2020	Japan	M/70	Unknown	Unknown	The amplitude of compound muscle action potentials was reduced, and the F wave's incidence was significantly reduced in the motor nerves (ulnar and median). In the sensory nerves (ulnar, median, and radial), the amplitude of sensory nerve potentials was in the lower limits of normal	After chemotherapy (combined with phlegmonous gastritis)	GBS: IVIG, 400 mg/kg/dx 5 d. Lymphoma: R-CHOP	Yes	[18]
12	2006	Spain	M/57	Unknown	Unknown	A severe reduction in amplitude of motor evoked potentials in the right peroneal and posterior tibial nerves, with a moderate decrease in the left median and cubital nerves	After chemotherapy	GBS: IVIG, 400 mg/kg/dx 5 dLymphoma: Splenectomy, CHOP, radiotherapy, R maintenance	Yes	[19]

DLBCL: Diffuse large B cell lymphoma; GBS: Guillain-Barré syndrome; IVIG: Intravenous immunoglobulin: R-CHOP: Rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone; AMSAN: Acute motor-sensory axonal neuropathy.