Table 1.
Haematological diseases in course of systemic sclerosis.
| First author/year | Number cases | Study type (country) | Age/sex | Dis. duration | Skin subset | Serology | Visceral inv. | Ass. Sjogren | History notes | Clinical picture | Hematological malignancy | Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Agard/2000 | 1 | CR (France) | 62 F | 14 | L | ACA | None | No | MGUS | Spleno/lymphoadenop., ascites | Small B cell NHL | Improved with CHOP |
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| Airo'/2011 | 1 | CS (360 Italian pts) | nd | nd | nd | ACA | nd | nd | nd | nd | NHL | nd |
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| Alacacioglu/2005 | 1 | CR (Turkey) | 57 M | 3 | nd | nd | nd | nd | nd | Bilateral upper/lower eyelid hernias | Orbital marginal zone NHL | Improved with chemo/radiotherapy |
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| Angeli/1991 | 1 | CR (France) | 42 F | 4 | L | ACA | nd | No | nd | Splenomegaly | CLL | nd |
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| Arai/2009 | 1 | CR (Japan) | 31 F | 1 | nd | nd | nd | nd | nd | None | Thymic large B-NHL | Remission with CHOP |
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| Arnaud/2006 | 1 | CR (France) | 76 F | 11 | L | nd | E | nd | H. pylori + | nd | Gastric MALT lymphoma | nd |
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| Bachleitner-Hofmann/2002 | 1 | CR (Austria) | 73 F | 14 | L | ACA | L, E | nd | MGUS | nd | MM | Marked and sustained improvement with therapy for MM and SSc |
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| Baldini/1994 | 1 | CR (Italy) | 59 F | 1 | nd | ANA | nd | nd | nd | nd | Lymphocytic Ly of intermediate diff. | Improved |
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| Bellis/2014 | 1 | CR (France) | 37 M | 1 | L | ANA | nd | nd | nd | Right axillary lymphoadenopathy | CD30+ anaplastic Ly | Lymphoma and SSc remission with BMT |
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| Ben Ghorbel/2005 | 1 | CR (Tunisy) | 70 F | 6 | L | Scl70 | L | No | nd | Generalized lymphoadenopaties | Follicular B NHL | Improved with CHOP |
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| Bielefeld/1996 | 5 | CS (21 French pts) | 39 F, 56 F, 69 F, 12 M, 71 M | 0, 6, 6, 9, 2 | nd | nd | nd | nd | nd | nd | CML, AML, immunocytoma, Burkitt's Ly, Waldenstrom d. | nd |
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| Bistue/1990 | 1 | CR (Argentina) | 36 F | nd | D | nd | L | No | nd | Dyspnea, splenomegaly, and fever | Myelofibrosis | nd |
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| Cavallero/1994 | 1 | CR (Italy) | 79 M | nd | D | ANA | nd | nd | Carpenter | Purpura of legs | Hairy cell leukemia | Died for pneumonia after 3 months |
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| Charlanne/2004 | 1 | CR (France) | 72 F | <1 | L | ACA | No | Yes | Overlap RA-SS | Neutropenia and lymphocytosis | Large granular lymphocyte leukemia | Sustained (>1 year) improvement with MTX 7.5/week for leukemia and autoimmunity |
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| Chatterjee/2005 | 5 | RS (538 US pts) | 2 NHL are F | nd | 2 NHL : 1 L, 1 D | nd | nd | nd | nd | nd | NHL (2); MM (2); leukemia (1) | nd |
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| Čolović/2011 | 1 | CR (Serbia) | 55 F | 20 | L | nd | nd | nd | nd | Intense facial pruritus, paraproteinemia | MM | Remission for SSc and MM |
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| Comer/1992 | 1 | CR (UK) | 31 F | 1 | L | ANA | E, L, H | No | nd | Neck/mediastinum lymphadenopathy | IIb-staged HL | HL remission (MOPP), SSc evolution by 1 year |
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| Constans/1993 | 1 | CR (France) | 65 F | 0 | L | ACA | CREST | No | nd | Hairy cell leukemia | nd | |
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| Derk/2003 | 1 | CR (USA) | 66 M | 2 | D | Scl70 | E | No | nd | Expanding mass at the tongue base | Large B-NHL | Remission with CHOP |
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| Doyle/1985 | 5 | CS (USA) | 10; 22; 31 54; 70 F | 4; 9; 9; 40; 57 | L | nd | CREST | nd | nd | nd | HL; MM (2); “malignant Ly”; CLL | Variable outcomes |
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| Duggal/2002 | 1 | CR (India) | 42 M | nd | nd | nd | nd | nd | nd | nd | HL | nd |
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| Duncan/1979 | 7 | CS (2,141 USA pts) | 50–79 F | 2, 0, 1, 3, 0, 61, 1 | nd | nd | nd | nd | nd | nd | CLL (3), MM, lymphosarcoma (2), CMML | Died by 1 year (2), alive > 5 years (4) |
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| Dupond/1989 | 1 | CR (France) | 73 F | nd | L | ACA | CREST, L | Yes | nd | Splenomegaly | CMML | nd |
| Ferroir/1991 | 1 | CR (France) | 42 M | 2 | nd | ANA | nd | No | nd | nd | Mixed follicular Ly | Diagnosis at autopsy |
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| Frigui | 1 | CR (France) | 56 F | 10 | L | Scl70 | L, K | No | nd | Skin lesion | Cutaneous B-cell Ly (supraorbital) | Regression after radiotherapy but relapse |
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| Gisser/1979 | 1 | CR (USA) | 29 F | 4 | nd | nd | L, H | nd | Previous chlorambucil treat. | Anemia | CML | Died for bronchopneumonia |
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| Hall/1978 | 1 | CR (USA) | 22 F | 14 | nd | nd | E calcinosis | No | Generalized lipodystrophy | Diffuse lymphoadenopathies | Nodular sclerosing HL | nd |
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| Hasegawa/1999 | 1 | CR (Japan) | 43 M | <1 | D | ANoA | nd | No | nd | Neck/armpits lymphoadenopathies | Diffuse large T cell NHL | Lymphoma and SSc remission (CHOP 4 cycles) |
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| Haviv/1997 | 1 | CR (Israel) | 72 F | 1, 5 | L | ANA | L, K | No | nd | Fever, wasting, and arthralgias | Diffuse small cell NHL | Death for sepsis |
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| Hill/2003 | 2 | RS (441 Australian pts) | F | nd | nd | nd | nd | nd | nd | nd | Not better specified | nd |
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| Hoshida/2004 | 7 | CS (Japan) | 57 (56–65), 2/5 M/F | 2.2 (0–12) | nd | nd | nd | 2/7 | nd | nd | HL (2); diffuse large B cell Ly (5) | All died by 1 year |
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| Kaşifoğlu/2006 | 1 | CR (Turkey) | 50 F | 7 | L | Scl70 | L | SSA+ | nd | Weakness, weight loss | CML | Improved with HU |
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| Kaşifoğlu/2016 | 3 | CS (340 Turkish pts) | nd | nd | nd | nd | nd | nd | nd | nd | MM, CML, follicular NHL | nd |
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| Katz/1979 | 1 | CR (USA) | 57 | 11 | nd | ANA | nd | nd | Pemphigus v. | nd | Diffuse histiocytic Ly | nd |
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| Kyndt/1997 | 1 | CS (123 French pts) | 76 F | 8 | nd | Scl70 | L | Yes | nd | nd | CMML | nd |
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| Kojima/2006 | 2 | CS (Japan) | nd | nd | nd | nd | nd | nd | nd | nd | B cell follicular Ly | nd |
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| Kuo/2012 | 6 | RS (2,053 Taiwanese pts) | 1 M, 5 F | nd | nd | nd | nd | nd | nd | nd | Ly (3), myeloprolif. dis. (2), CML (2) | nd |
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| Lee/2001 | 1 | CR (Korea) | 56 F | 15 | L | ACA | CREST | No | Porphyria c.t. | Splenomegaly | Myelofibrosis | nd |
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| Marto/2014 | 1 | CR (Portugal) | 76 F | 0 | L | ACA | L | No | Multiple polyps of the colon | Multiple adenop., diarrhea, and rectorrhagia | IIIb-staged mantle cell NHL of the colon | Ly remission with R-CHOP |
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| Miyamoto/2000 | 1 | CR (Japan) | 55 F | 17 | nd | nd | nd | No | nd | Fever, fatigue, pancytopenia, and splenomegaly | Myelofibrosis | Treated with pulse steroids and transfusions |
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| Olesen/2010 | 18 | RS (2,040 Danish pts) | M/F 9/9 | 2/18 : <1 | nd | nd | nd | nd | nd | nd | NHL (10); leukemia (7) | nd |
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| Owlia/2014 | 1 | CR (Iran) | 58 M | 15 | L | nd | E | No | smoker (30 p-y) | Lumbar pain (extensive bony infiltration) | MM | Death 2 years after VAD/bortezomib |
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| Ozturk/2006 | 1 | CR (Turkey) | 54 F | 5 | L | nd | CREST | No | nd | Sweet syndrome | Myelofibrosis | Improved with steroids and hydroxyurea |
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| Parma/1996 | 1 | CR (Italy) | 68 | 3 | nd | nd | nd | nd | nd | Primitive muscle and bone involv. | Large multilobated B-cell NHL | Improved |
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| Prochorec-Sobieszek/2004 | 1 | CR (Poland) | 22 F | <1 | L | PmScl | nd | No | nd | Parotid swelling | Parotid MALToma | nd |
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| Rodrigues/1989 | 1 | CR (Brazil) | nd | nd | nd | nd | nd | nd | Concom. thyroid adenoca. | nd | Ileal B-cell Ly | Rapid deterioration until death |
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| Rosenthal/1993 | 3 | RS (233 Swedish pts) | nd | <1 (1) | nd | nd | nd | nd | nd | nd | NHL (2), not better specified hematological cancer (1) | nd |
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| Rothfield/1992 | 1 | CS (148 USA pts) | nd | nd | nd | Scl70 | nd | nd | nd | nd | Lymphocytic Ly | nd |
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| Roumm/1985 | 3 | CS (262 USA pts) | 33 F, 50 F, 71 F | 3.5, 6.5, 5.5 | nd | nd | nd | nd | nd | nd | CML, AML, and histiocytic Ly | nd |
| Ryczek/2013 | 1 | CR (Poland) | nd | nd | nd | nd | nd | nd | nd | nd | CML | nd |
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| Schnack/1954 | 1 | CR (Austria) | 53 F | 8 | D | nd | nd | nd | nd | nd | MM | nd |
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| Senel/2006 | 1 | CR (Turkey) | 65 F | 0 | D | Scl70 | L, K | No | nd | Weakness, sweating, and weight loss | CML | nd |
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| Shvidel/2002 | 1 | CS (Israel) | 71 F | nd | nd | nd | nd | nd | nd | nd | T large granular lymphocytic leukemia | nd |
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| Siau/2011 | 5 | CS (68 UK pts) | nd | 0 (case of PC) | L | nd | nd | nd | nd | nd | MM (2), diffuse large B-NHL, thyroid NHL, solitary IgM PC | nd |
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| Sidi/1990 | 2 | CS (Israel) | 47 M, 77 M | 20; 11 | L | nd | CREST | No | nd | Generalized lymphoadenopathy | B-CLL | Alive up to 2 years; death for bronchopneumonia and paralytic ileus |
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| Sugai/1987 | 1 | CR (Japan) | 67 F | 11 | D | ANA | E, L | Yes | nd | Parotid swelling and generalized lymphadenopathy | IIIb-staged NHL | Death after 3 COPP cycles for complicating interstitial pneumonitis |
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| Suzuki/1994 | 1 | CR (Japan) | 68 M | 3 | D | ANA | nd | No | nd | Gait disturbance, anemia, and hemorrhagic stroke | Brain diffuse large B-NHL | Death for pneumonitis during BACOPP chemotherapy |
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| Szekanecz/2008 | 3 | CS (218 Hungarian pts) | 53; 67; 69 F | 2; 1.9; 0.7 | D | Scl70; | L-H-E; none; L-H-K-E | nd | nd | nd | (2) b-CLL; (1) chronic small lymphocytic B NHL | Surviving > 5 years |
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| Talbott/1979 | 2 | CS (USA) | 64 M; 73 M | <1; 10 | L; D | nd | None; L-H | Probable | Pt number 1 coal miner | Backache; generalized weakness | MM | Rapid deterioration and death |
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| Vettori/2010 | 1 | CR (Italy) | 45 F | Sine sclerod. | Progressive weight loss | Gastric B-cell Ly | ||||||
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| Watanabe/1994 | 1 | CR (Japan) | 44 F | nd | nd | nd | nd | nd | nd | Leukocytosis, thrombocytosis | CML | CML remission and SSc improvement with therapy |
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| William/2011 | 1 | CR (USA) | 61 M | 30 | L | ACA | E, L | No | nd | Thrombocytopenia, cervical adenopathy | Small lymphocytic B-NHL | Remission with FCR |
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| Wooten/1998 | 1 | CR (USA) | nd | 3 | L | CREST | nd | Porphyria c.t. | nd | CML | nd | |
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| Yamamoto/2005 | 1 | CR (Japan) | 72 M | 5 | D | Scl70 | L | nd | nd | Multiple lymphoadenopathy | Angioimmunobl. T cell Ly with EBV-assoc. B cell lymphoprol. dis. | Died 6 months after CHOP therapy because of sepsis, initially improved |
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| Present study | 2 | CR (Italy) | 37 M; 72 F | 2; 28 | D; L | SSA/SSB ACA | E, L; CREST + L | Yes; no | nd; previous breast cancer | Weakness, sweating, and weight loss; asymptomatic | Diffuse large B-NHL; marginal B-NHL | Died few months after during R-CHOP therapy; lung lobe resection and remission |
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| Total | 130 pts | |||||||||||
The table included all the case reports and the cohort studies that reported cases of haematological malignancies in the course of SSc [4–67]. Pts = patients; type of study: CR = case report; CS = case series/cohort studies; RS = registry studies; skin subset: D = diffuse, L = limited; serology: ACA = anticentromere, Scl70 = anti-topoisomerase I, ANA = specific antinuclear autoantibodies; organ involvements: K = kidney, L = lung, H = heart, E = esophagus; MGUS = monoclonal gammopathy of undetermined significance; CREST = former acronym for limited SSc form including calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia; CLL = chronic lymphocytic leukemia; CML = chronic myelogenous leukemia; AML = acute myelogenous leukemia; MM = multiple myeloma; PC = plasmacytoma; NHL = non-Hodgkin lymphoma; CMML = chronic myelomonocytic leukemia; Ly = lymphoma; HL = Hodgkin lymphoma; MTX = methotrexate; (R-)CHOP = chemotherapic regimen for NHL; FCR = chemotherapic regimen with fludarabile, cyclophosphamide, and rituximab; BMT = bone marrow transplantation; (BA)COPP = bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone; MOPP = mustine, vincristine, procarbazine, and prednisone; HU = hydroxyurea; VAD = vincristine, doxorubicin, and dexamethasone.