Table 1.

Summary of clinical and laboratory results of cases investigated.

Thyroid lobe involved	Diagnosis	Clinical stage	Serology	Immunophenoytpe	NGS‐based IG clonality analysis	Genetic changes and tumour clonal evolution*		Treatment	Clinical outcome
Case 1: 67‐year‐old female with 5‐year history of HT
Right lobe	Original diagnosis of HT, but EMZL on review	IE	TgAb+ TPOAb+	CD10−, BCL6−, BCL2+	Clonal IGHV4‐34/JH6 (FR1‐JH primers)	BCL2 trans−ve BCL6 trans−ve	Shared mutations: 2 Unique mutations: 14 in first lesion, 14 in second lesion	Right lobectomy	Progressed to EMZL 36 months later
Left lobe	EMZL	IE	TgAb+	CD10−, BCL6−, BCL2+	Failed to amplify	BCL2 trans−ve BCL6 trans−ve	Evolution: divergent from clonally related lymphoma precursor cells	Total residual resection and local radiation (30.6 Gy)	CR and alive at last follow‐up (15 months after treatment)
Case 2: 59‐year‐old female with 2‐year history of HT
Left lobe	Original diagnosis of HT, but EMZL on review	IE	TgAb+ TPOAb+	CD10−, BCL6−	Identical clonal IGKVD3‐20/JK2 rearrangement (IGK Tube A)	BCL2 trans−ve BCL6 trans−ve	Shared mutations: 17 Unique mutations: 1 in first lesion, 4 in second lesion	n/a	Open biopsied (resection), otherwise no other active treatment, but progressed to EMZL 31 months later
Both lobes	EMZL	IE	TgAb+ TPOAb+	n/a		BCL2 trans − ve BCL6 trans − ve	Evolution: divergent from clonally related lymphoma precursor cells	Total thyroidectomy	CR and alive at last follow‐up (18 months after treatment)
Case 3: 76‐year‐old female with 6‐year history of HT
Right lobe	EMZL	IE	TgAb+ TPOAb+	CD10−, BCL6−, MYC+ (<5%)	Failed to amplify	BCL2 trans−ve BCL6 trans−ve MYC trans −ve	Shared mutations: 3 Unique mutations: 14 in first lesion, 106 in second lesion	Local radiation (38 Gy)	Achieved CR, but relapse 8 years later
Right lobe	DLBCL	IIE	TgAb‐ TPOAb+	CD10−, BCL6+, MUM1−, MYC+ (~70%)	Clonal IGHV3‐15/JH4 rearrangement (FR2‐JH primers)	BCL2 trans−ve BCL6 trans−ve IGH::MYC trans +ve	Evolution: divergent from clonally related lymphoma precursor cells	R‐CHOP × 6	Achieved CR, died of infection due to MDS 36 months later
Case 4: 57‐year‐old male with HT diagnosed together with initial lymphoma
Right lobe	DLBCL	IIE	TgAb+	CD10+, BCL6+, BCL2+, MUM1−, MYC+ (~50%)	Identical clonal IGHV3‐7/JH4 rearrangement (FR2‐JH primers)	BCL2 trans−ve BCL6 trans−ve	Shared mutations: 1 Unique mutations: 14 in first lesion, 10 in second lesion	Local radiation (36 Gy) and R‐CHOP	Achieved CR, but lymphoma relapsed 7 years later
Left lobe	DLBCL	IIIE	TgAb+ TPOAb‐	CD10+, BCL6+, MYC+ (~15%), MUM1−		BCL2 trans−ve BCL6 trans−ve	Evolutionary: divergent from clonally related lymphoma precursor cells	R‐ICE × 2, followed by BMT	Achieve CR, alive at last follow‐up (29 months after treatment)
Case 5: 65‐year‐old female with no previous history of HT
Left lobe	EMZL	IE	TgAb− TPOAb−	CD10−, BCL2+, BCL6−	Failed to amplify	BCL2 trans−ve BCL6 trans+ve	Shared mutations: 21 Unique mutations: 1 in second lesion	Local radiation (36 Gy)	Achieved PR, but disease progressed 10 months later
Right lobe	EMZL	IE	TgAb+ TPOAb‐	CD10−, BCL6−, BCL2+		BCL2 trans−ve BCL6 trans+ve	Evolution: linear progression	Total thyroidectomy & R‐CHOP x 3	Achieved CR, alive at last follow‐up (57 months after treatment)
Case 6: 60‐year‐old female with 39‐year history of HT, positive for EBV
Right lobe	EMZL	IIE	TgAb+ TPOAb+	CD10−, BCL6+, MYC+ <5%, EBER negative	n/a	BCL2 trans−ve BCL6 trans−ve MYC trans−ve	Shared mutations: 23 Unique mutation: 20 in second lesion	R‐CHOP (number of cycle unknown)	CR and alive at last follow‐up (39 months after treatment)
	DLBCL			CD10−, BCL6+, MYC+ (~30%), EBER positive		BCL2 trans−ve BCL6 trans−ve MYC trans+ve	Evolutionary: linear progression
Case 7: 73‐year‐old female with 4‐month history of HT
Both lobes	FL3A	IIE	TgAb+ TPOAb‐	CD10−, BCL6+, BCL2+	n/a	BCL2 trans−ve BCL6 trans−ve	Shared mutations: 1 Unique mutation: 28 in first lesion, 1 in second lesion	R‐CHOP×3	Achieved CR, then suspicious lymphoma relapse 48 months later
Both lobes	HT	n/a	TgAb+	n/a		BCL2 trans−ve BCL6 trans−ve	Evolutionary: divergent from clonally related lymphoma precursor cells	Watch and wait	Alive at last follow‐up (35 months after treatment)
Case 8: 62‐year‐old female with 2‐year history of HT
Left lobe	HT	n/a	TgAb+ TPOAb+	n/a	Identical clonal IGKV1‐12/KDE rearrangement (IGK tube B)	n/a	Shared mutation: 8 Unique mutation: 9 in first lesion, 10 in second lesion	n/a	Progressed to EMZL 5 years later
Right lobe	EMZL	IE	n/a	CD10−, BCL6−		BCL2 trans−ve BCL6 trans−ve	Evolutionary: divergent from clonally related lymphoma precursor cells	Local radiation (34 Gy)	CR and alive at last follow‐up (48 months after treatment)
Case 9: 71‐year‐old female with a 30‐year history of HT
Left lobe	HT	n/a	TgAb‐ TPOAb+	n/a	n/a	n/a	No mutations identified	n/a	Progressed to EMZL 12 months later
Left lobe and small low echoic spots in right lobe	EMZL	IE	n/a	CD10−, BCL6−		BCL2 trans−ve BCL6 trans−ve	28 unique clonal mutations	Total thyroidectomy	CR and alive at the last follow up (8 months after treatment)
Case 10: 73‐year‐old female with no previous history of HT
Left lobe	HT	n/a	TgAb+ TPOAb+	n/a	n/a	n/a	No mutations identified	n/a	Progressed to EMZL 36 months later
Left lobe	EMZL	IIE	TgAb+ TPOAb+	CD10−, BCL6−, BCL2+		BCL2 trans−ve BCL6 trans+ve	59 unique clonal mutations	Total thyroidectomy and local radiation (50Gy)	CR and alive at last follow‐up (7 months after treatment)

Abbreviations: BMT, bone marrow transplantation; CR, complete remission; DLBCL, diffuse large B‐cell lymphoma; EBV, Epstein–Barr virus; trans+ve: translocation positive; trans−ve: translocation negative; EMZL, extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue; FL, follicular lymphoma; HT, Hashimoto's thyroiditis; MDS, myelodysplastic syndromes; n/a, not available; PR, partial response; TgAb, thyroglobulin antibody; TPOAb, thyroid peroxidase antibody.

^*Only clonal variants with a variant allele frequency (VAF) >0.05 were included for lymphoma lesions, while all variants, including those seen in paired lymphoma specimens regardless of their VAF, were considered for the HT lesion.