CD8-positive indolent T-Cell lymphoproliferative disorder of the gastrointestinal tract: A case report and review of literature

Table 1 Case reports of CD8+ Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract

Ref.		Country	Age	Gender	Involved sites	Clinical presentation	Endoscopic findings	IHC/ Phenotype/molecular		Molecular/Genetic alterations		Treatment	Follow-up (mo)
								Positive	Negative	Rearrangement	Other gene
Tsutsumi et al[8], 1996		Japan	48	Male	Small bowel	Abdominal distension, diarrhea, weight loss, leg edema	Irregular granular mucosa	CD2, CD3, CD5, CD8, TCRβ, HLA-DQ, HLA-DR	CD4, CD20, TCRδ, EBER	Q3-1 region	NA	None	AWD (12)
Ranheim et al[11], 2000		United States	35	Male	Palate, small bowel, colon, rectum	Recurrent oropharyngeal ulcer, rectal bleeding	Small erosions in colonic mucosa	CD3, CD5, CD8, TCRαβ	CD4, CD56, TIAI	TCRγ	NA	None	AWD (108)
Leventaki et al[15], 2013		United States	42	Male	Esophagus, stomach, small bowel, colon, bone marrow	Peptic ulcer	Nodular gastric and duodenal mucosa	CD2, CD3, CD8, GRZB (subset), Ki67 < 10%	CD4, CD5, CD56, CD57	TCRβ/γ	NA	IFN, Ia, Ster	AWD (237.6)
Perry et al[25], 2013	United States		15	Female	Small intestine (jejunum, ileum), colon	Abdominal pain, diarrhea	Numerous small polyps, erosions	CD2, CD3, CD5, CD7, CD8, TIA1, TCRβ; Ki67: 5%-10%	CD30, CD56, GRZB, EBER	TCRγ	STAT3 mutation(-)	CHOP (3)	AWD (52)
			31	Male	Small intestine (ileum), colon	Diarrhea	Numerous small polyps, erythema	CD2, CD3, CD5, CD7, CD8, TIA1, Ki67: 5%-10%	CD30, CD56, GRZB, EBER			NA	AWD (17)
			35	Male	Oral cavity, small intestine (ileum), colon	Oropharyngeal ulcers, rectal bleeding	NA	CD3, CD5, CD8, TIA1, TCRβ	CD56, TCRG, EBER			None	AWD (156)
			38	Male	Esophagus, stomach, small intestine (duodenum, ileum), colon	Abdominal pain, diarrhea, food intolerance	Stomach: unremarkable; duodenum: thickend folds	CD2, CD3, CD5, CD7, CD8, TIA1, TCRβ, Ki67: 5%	CD30, CD56, TCRG, EBER			NA	AWD (14)
			52	Female	Stomach	Abdominal pain, vomiting, diarrhea	NA	CD3, CD5, CD8, TIA1, Ki67: 5%	CD7, CD56, GRZB, EBER			Unknown chemothery	AWD (24)
			52	Male	Colon	Abdominal pain, bloody diarrhea	Congestion, erythema and friable mucosa	CD3, CD5, CD8, T1A1, TCRβ, Ki67: 5%	CD7, CD30, CD56, GRZB, TCR-G, EBER			CHOP (4)	AWD (175)
			59	Female	Small intestine (duodenum)	Abdominal bloating, diarrhea, foul stools; hypocalcemia, hypoka, hyp	“Irregular” appearace of duodenal mucosa	CD2, CD3, CD5, CD7, CD8, Ki67: 5%	CD30, CD56, GRZB			None	AWD (23)
			77	Female	Oral cavity, small intestine (ileum)	Oropharyngeal ulcers; history of Crohn disease	NA	CD2, CD3, CD5, CD7, CD8, TIA1, GRZB, TCRβ, Ki67: 5%	CD30, CD56, EBER			NA	AWD (168)
Edison N et al[20], 2016		Israel	27	Female	Sigmoid colon, ascending colon, cecum	History of IBD	Consistent with IBD	CD2, CD3, CD5, CD7, CD8, TCRβ, TIA1	CD56, CD57, GRZB	TCRG, TCRB	NA	5Aa, Ster, Aza, Ada	NA
Wang et al[21], 2017		China	39	Male	Colitis, caecum, rectum, renal	Chronic diarrhoea, loss of weight, poly arthralgia, intermittent fever	Erythema and friable mucosa	CD2, CD3, CD7, CD8, TIA1, TCRβ	CD4, CD10, CD20, CD56, TCRγ, CD30, GRZB, ALK1, EBER	TCRγ	NA	Bas, Tac, Ster, Aza, Ami, Mes	NA
Sharma et al[19], 2018		United States	47	Female	Stomach, duodenum, jejunum, ileum	NA	NA	CD3, CD5, CD8, T1A1, TCRβ, Ki67: 5%, P-STAT5 (Y694)	CD4, CD7, CD56, GRZB, TCRγδ	NA	STAT3-JAK2 fusion (-)	NA	NA
			39	Male	Stomach, duodenum, jejunum, ileum, colon	NA	NA	CD3, CD5, CD7, CD8, T1A1, TCRβ	CD4, CD56, GRZB, TCRγδ
			74	Female	Duodenum, jejunum	NA	NA	CD3, CD5, CD7, CD8, T1A1, TCRβ, P-STAT1 (Y694)	CD4, CD56, GRZB, TCRγδ
			57	Male	Ileum	NA	NA	CD3, CD5, CD7, CD8, T1A1, TCRβ	CD4, CD56, GRZB, TCRγδ
Guo L et al[26], 2019		China	46	Male	Intestine	Paraumbilical colic pain, bloating, occasional diarrhea	Diffuse small nodular hyperplasia, irregular ulcers and intestinal stricture, granulate mucosa and redness	CD2, CD3, CD5, CD8, CD43, Ki67: 5%	CD4, CD20, CD56, GB	TCRγ	NA	CHOP (8), Rit (3)	AWD (6)
Kohri M et al[27], 2019		Japan	52	Male	Colon	Diarrhea	Diffuse edematous lesions with multiple aphtha	CD3, CD5, CD7, CD8, TIA1, Ki67 < 10%	CD4, CD56, EBER	NA	NA	CyclOBEAP	AWD (79)
Moreno et al[29], 2019		Spain	68	Female	None	History of IBD/IBS	Normal	CD2, CD3, CD5, CD7, CD8, TIA1, TCRβ, GRZB (subset), CD103 (subset), EBER, Clonal TCR, Ki67 < 10%	NA	NA	STAT3-JAK2 fusion (-)	Aza, Anti, Ster, CHOP	NA
Saggini A et al[28] 2020		Italy	65	Male	Oral, tongue, larynx, colon	2-cm-wide infiltrated, enlarging, non-ulcerated plaque	NA	CD2, CD3, CD5, CD8, CD20, TIA1, TCRβ, Ki-67 < 5%	CD4, CD56, PAX5, CD79a	TCRγ	NA	Cor	AWD (36)
			36	Male	Intestinal and lymph node	Malabsorption, weight loss	NA	CD3, CD5, CD7, CD8, TIA1, Ki67 < 5%	CD4, CD56, EBER Clonal TCR	NA	STAT3-JAK2 fusion (-)	Aza, Anti, Ster, CHOP	NA
Soderquist et al[30] 2020		United States	38	Male	Duodenum, jejunum, ileum, colon	Diarrhea, abdominal pain, vomiting	Mucosal nodularity, decreased, duodenal folds, gastric erythema	CD2, CD3, CD5, CD7, CD8, CD103, TCRαβ, Ki-67 < 5%, GATA3	CD4, CD30, CD56, TIA1, TCRγδ, T-bet, GRZB	NA	IL2-RHOH	None	AWD (252)
			38	Male	Duodenum, ileum, colon	Diarrhea, weight loss, abdominal pain	Mucosal nodularity, erythema, friability	CD2, CD3, CD5, CD7, CD8, CD103, TIA1, TCRαβ, Ki-67 < 5%, GATA3, T-bet	CD4, CD30, TCRγδ	NA	IL2 3’ UTR deletion, IL2-TNIP3	CP, Dox, VCR, Bud, Pred, Etop, AGS67E	AWD (84)
			41	Male	Duodenum, stomach, bone marrow	Abdominal pain	Mucosal nodularity, decreased duodenal folds	CD2, CD3, CD8, TIA1, TCRαβ, Ki-67 < 5%, GATA3	CD4, CD5, CD30, CD56, CD103, GRZB, TCRγδ	NA	None identified	IFN, CP, Dox, VCR, Pred, Gem	Dead (324)
			49	Male	Duodenum, jejunum	Diarrhea weight loss, abdominal pain, Crohn’s disease	Flattened small bowel mucosa, gastric erythema	CD2, CD3, CD5, CD7, CD8, TIA1,TCRαβ, Ki-67 < 5%, GATA3	CD4, CD30, CD103, TCRγδ, T-bet	NA	None identified	CP, Dox, VCR, Pred, Mes, Aza	AWD (228)
Takahashi et al[31], 2020		Japan	70	Female	Stomach	Mild epigastralgia, weight loss	Multiple erosions in the lower body	CD3, CD5, CD8, CD43, TIA1, GRZB, TCRβ, Ki-67: 10%	CD4, CD56, EBER	NA	NA	IFRT	NA
Thomas SJ et al[23], 2020		United Kingdom	31	Female	Uterine corpus	Menorrhagia, anemia	NA	CD2, CD3, CD5 CD7, CD8, TCRβ, TIA1	CD5, CD10, CD21, CD23, CD56, ALK1, EBER	NA	Oe	Local lesection	NA
Wu et al[32], 2020		China	42	Male	Rectum, colon	Dental ulcers, abdominal pain, and diarrhea	Rough, hyperemic, mucosa, multifocal deep ulcers	CD3, CD8, CD43, TIA1, Ki-67: Approximately 5%–10%	CD4, CD5, CD20, CD56, TdT, EBER	TCRγ	NA	Mes, Cg, Pcb	AWD (12)

5Aa: 5-Aminosalycilic acid; Ada: Adalimumab; Cg: Compound glutamine; AGS67E: Ant, antibiotics Anti-CD37 monoclonal antibody AGS67E; Ami: aminosalicylate sulfasalazine; AWD: Alive with disease; Aza: Azathioprine; Bas: Basiliximab; Bud: Budesonide; CHOP: Chronic abdominal pain; Cor: Corticosteroids; CP: Cyclophosphamide; CyclOBEAP: Cyclophosphamide, doxorubicin, vincristine, etoposide, bleomycin and prednisone; Dox: Doxorubicin; EBER: Epstein-Barr virus-encoded RNA; Etop: Etoposide; GRZB: Granzyme B; Gem: Gemcitabine; Hyp: Hypozincemia associated with paraesthesias, confusion; Hypoka: Hypokalemia; Ia: Isotretinoic acid; IFN: Interferon; IFRT: Involved field radiotherapy; ITLPD-GI: Indolent T-cell lymphoproliferative disease of the gastrointestinal tract; Mes: Mesalamine; Oe: Oligoclonal expansion; Pcb: Probiotic cocktail Bifico; Pred: Prednisone; Rit: Rituximab; Ster: Steroid; Tac: Tacrolimus; TCR-BF1: T-cell receptor b F1; TCRG: T-cell receptor g; VCR: Vincristine; NA: Not available.

Table 2 The number and proportion of case reports

Age		Gender		Involved sites	Number	Proportion	Clinical presentation	Number	Proportion	IHC/ Phenotype/Molecular
											Positive	Negative
< 45	15	Male	19	Small intestine	18	62.10%	Chronic abdominal pain	11	37.90%	CD2	17	0
										CD3	29	0
				Colon	14	48.30%				CD4	0	18
							Diarrhea	14	48.30%	CD5	25	3
				Stomach	6	20.70%				CD7	17	3
≥ 45	14	Female	10							CD8	29	0
				Oral cavity	4	13.80%	Weight loss	6	20.70%	CD56	0	25
										TCRαβ	21	0
				Esophagus	4	13.80%				T1A1	23	2
										EBER	1	14

IHC: Immunohistochemistry; EBER: Epstein-Barr encoding region.