Hemophagocytic Lymphohistiocytosis in Association with Primary Cutaneous Anaplastic Large Cell Lymphoma

Table 1

Comprehensive review on lymphoma associated hemophagocytic lymphohistiocytosis (HLH).

		With HLH ()	Without HLH ()	value	Remark
Xie et al. [4], (peripheral T cell lymphoma)	Age (years), range, mean	16–78 (48)	10–77 (46)	—	Most common histological types,; PTCL-NOS; Less Common types,; AITL, SCPTCL, NKTCL; prognosis is poor in HLH group.; High   microglobulin, CA-125 are important biomarkers in T-NHL associated HLH.
	Male/female	23/13	86/17	—
	Stage III/IV, number, %	34/36 (94%)	93/123 (76%)	0.013
	B symptoms	100%	76%	0.001
	Fever	92%	43%	<0.001
	Organomegaly	72%	23%	<0.001
	Bicytopenia	78%	13%	<0.001
	Bone marrow involvement	56%	26%	<0.002
	Median survival	3 months	16 months	—
	Overall survival (log rank test)	11%	44%	<0.001
	Biochemical parameters
	microglobulin (>2200 mcg/L)
	Ferritin (>500 pg/mL)
	Fibrinogen (<1.5 g/L)
	Liver dysfunction	More common	Less common	<0.003
	CA-125 (>35 IU/L)
	Triglyceride (>265 mg/dL)			0.015
	Lactate dehydrogenase (>225 mg/dL)			>0.05
		With HLH	Without HLH		Remark
Tong et al. [11] (T cell NHL)	Number ()	28/113	85/113		Fever, raised LDH, ferritin, CA-125, microglobulin, hepatosplenomegaly, cytopenias are more in favor of T cell lymphoma associated HLH.
	Elevated lactate dehydrogenase	100%	55%
	High ferritin	100%	64%
	Fasting hypertriglyceridemia	79%	43%
	Hypofibrinogenemia	43%	14%
	Bone marrow involvement	57%	32%
	Liver dysfunction	40%	13%
	Median survival	40 days	8 months
Han et al. [12] (, lymphoma associated HLH)	Male/female, 16/13; Age, 46 years (9–87); 14, high-intermediate IPI, 12, high IPI	Neutropenia, 11/29 (37.9%), thrombocytopenia, 25/29 (86.2%),; Hb < 90 g/L, 16/29 (55.2%), ferritin >2000 pg/mL, 13/14, LDH > 500 IU/L, 26/26, low fibrinogen, 15/26 (57.7%), DIC, 16/29.; Histological subtypes: EN-NKTCL (37.9%), PTCL-NOS (27.6%), DLBCL (17.2%), ALCL (ALK-) (6.9%).			Median survival = 36 days; DIC, jaundice, T/NK cell phenotype; poor clinical response-bad markers.; 12/17; EBV positive.
	With bone marrow involvement ()	Without bone marrow involvement ()		value	Remark
Tong et al. [13] (, peripheral T cell NHL)	Lymphoma associated HLH, 25/70 (36%)	Lymphoma associated HLH, 8/103 (8%)		<0.001	Common histological subtypes with bone marrow involvement: AITCL, PTCL-NOS, ALCL, EN-NKTCL, EATCL
	High ferritin and liver dysfunction: common	Less common		<0.05
	Anemia: 51%	29%		0.001
	1 year overall survival: 5%	49%
Ménard et al. [5] (, Hodgkin lymphoma associated HLH)	Males/females, 26/6, M : F = 3.3 : 1; Age = 43 years (19–84 years),; 26, HIV nonreactive, 8, HIV +ve.; 100%, stage IVB	9/20 (45%), lymphocyte depleted,; 8/20 (40%), mixed cellularity,; 3/20 (15%), nodular sclerosis subtype; 32/34 (92%) cases +ve for EBER (ISH), LMP-1 (IHC), ZEBRA −ve in all			HL-HLH strongly associated with EBV.; Prognosis not studied.; High levels of LMP-1 expression may induce the large amount of; Th1 cytokines production by Reed Sternberg cells leading to HLH.
			B-NHL-HLH	NKTCL-HLH	Remark
Takahashi et al. [14], Japan, (, lymphoma associated HLH)	Number (); Median age at diagnosis; Cytopenia(s), coagulopathy, liver dysfunction; Intravascular lymphomatosis; Hepatosplenomegaly; Lymphadenopathy; EBV positivity (ISH); Median survival (days)		68; 63.5 years; less common; 10/20; +; Nil; 3/24; 242	74; 49 year; more common; —; +; +; 19/23; 69	Prognosis is better in B-NHL associated HLH than NKTCL associated HLH.

HLH: hemophagocytic lymphohistiocytosis, PTCL-NOS: peripheral T cell lymphoma, not otherwise specified, AITL: angioimmunoblastic T cell lymphoma, SCPTCL: subcutaneous panniculitis-like T cell lymphoma, EN-NKTCL: extranodal natural killer/T cell lymphoma, T-NHL: T cell non-Hodgkin lymphoma, EATCL: enteropathy associated T cell lymphoma, ALCL: anaplastic large cell lymphoma, ALK: anaplastic lymphoma kinase, DLBCL: diffuse large B cell non-Hodgkin lymphoma, not otherwise specified, B-NHL-HLH: B cell non-Hodgkin lymphoma associated HLH, NKTCL-HLH: natural killer cell T cell lymphoma associated HLH, IPI: international prognostic index, LDH: lactate dehydrogenase, DIC: disseminated intravascular coagulation, EBV: Epstein Barr virus, EBER: Epstein Barr encoding region, ISH: in situ hybridization, LMP: latent membrane protein, and IHC: immunohistochemistry.