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Epidemiology

Novel invariant features of Good syndrome

Leukemia volume 35, pages 1792–1796 (2021)Cite this article

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Good syndrome (GS), originally described in 1954 by Dr Robert Good in a series of three patients, classically comprises hypogammaglobulinemia (HG) and thymoma [1]. We encountered a challenging 85-year-old patient with 5 months duration of normocytic, normochromic, reticulocytopenic anemia, a thymoma, and HG, compatible with a provisional diagnosis of pure red cell aplasia (PRCA). A blood smear revealed reactive large granular lymphocytic (LGL) leukemia with an absolute LGL count of 2020/µL. A bone marrow aspiration/biopsy showed a paucity of erythroid precursors, increased myeloid/erythroid ratio, no dysplastic changes, nor cytogenetic abnormalities suggestive for a concomitant myelodysplastic syndrome and CD8+ lymphocytic infiltrates negative for somatic STAT3/STAT5B mutations. Flow cytometry demonstrated increased CD56+CD16+CD8+ cells with a positive TCR-gamma rearrangement. This presentation resembled GS, with the additional presence of PRCA and LGL. We subsequently identified two additional cases, both presenting with the combination of GS, PRCA, and LGL, TCR-gamma rearrangement but no bone marrow dysplasia, cytogenetic abnormalities, STAT3/STAT5B, or other myeloid mutations. Of note, all these three patients were male and two of them presented with lichen planus, a chronic autoinflammatory disorder that most often affects middle-aged adults, involving both the skin and mucous membranes. While the association between LGL and PRCA has been previously studied [2, 3], to the best of our knowledge, only one patient with coexisting GS and LGL has been reported [4]. This suggests that our series did not represent a random combination of rare clinical features, pointing instead to common pathogenetic links. They may include regulatory circuits involving precursor B- and T-cell maturation and thymic epithelium function explaining coexistence of HG, T-cell autoimmunity, and propensity for clonal expansion [5]. This report investigates whether GS associations constitute a novel continuum of clinical features with unifying pathogenesis.

Our initial series of three index patients with the fully blown tetrad of thymoma, HG, PRCA, and LGL (Fig. 1C) inspired a systematic review of similar cases seen by our service among the aforementioned three cohorts of patients (Fig. 1A). In addition to the initial cases, 21 patients with GS were identified for a total of 24 patients (median age at diagnosis of GS was 60 years, see also Table 1). Among patients with GS, PRCA had a total frequency of 30%, while within the cohorts of thymoma and LGL, isolated PRCA was present in 7% of cases. (Fig. 1B, Table 1). Overall, the prevalence of GS was 7.3% in thymoma, 9.4% in PRCA, and 1% in LGL cohorts. An additional case of lichen planus was also noted for a total of 3/24 within the cohort of all GS cases (Fig. 1C, Table 1). With a median follow-up of 64 months (range, 0.4–227), the 5-year overall survival for these patients was 66% (95% confidence interval: 47.9–90.5; see Fig. 1D).

Table 1 Demographic and hematological characteristics of patients with “Good syndrome”.
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Fig. 1: Overlapping relationships between Good syndrome, large granular lymphocytic leukemia, and pure red cell aplasia.

References

  1. Good RA. A provocative experiment of nature. Bull Uni Minn Hosp Minn Med Found. 1954;26:1–19.

    Google Scholar 

  2. Balasubramanian SK, Sadaps M, Thota S, Aly M, Przychodzen BP, Hirsch CM, et al. Rational management approach to pure red cell aplasia. Haematologica. 2018;103:221–30.

    Article  CAS  Google Scholar 

  3. Go RS, Li C-Y, Tefferi A, Phyliky RL. Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes. Blood. 2001;98:483–85.

    Article  CAS  Google Scholar 

  4. Caperton C, Agrawal S, Gupta S. Good syndrome presenting with CD8(+) T-Cell large granular lymphocyte leukemia. Oncotarget. 2015;6:36577–86.

    Article  Google Scholar 

  5. Kelleher P, Misbah SA. What is Good’s syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56:12–6.

    Article  CAS  Google Scholar 

  6. Suster S, Moran CAThymoma. atypical thymoma, and thymic carcinoma. A novel conceptual approach to the classification of thymic epithelial neoplasms. Am J Clin Pathol. 1999;111:826–33.

    Article  CAS  Google Scholar 

  7. Jansen A, van Deuren M, Miller J, Litzman J, de Gracia J, Saenz-Cuesta M, et al. Prognosis of Good syndrome: mortality and morbidity of thymoma associated immunodeficiency in perspective. Clin Immunol. 2016;171:12–7.

    Article  CAS  Google Scholar 

  8. Sanikommu SR, Clemente MJ, Chomczynski P, Afable MG, Jerez A, Thota S, et al. Clinical features and treatment outcomes in large granular lymphocytic leukemia (LGLL). Leuk Lymphoma. 2018;59:416–22.

    Article  Google Scholar 

  9. Durrani J, Awada H, Kishtagari A, Visconte V, Kerr C, Adema V, et al. Large granular lymphocytic leukemia coexists with myeloid clones and myelodysplastic syndrome. Leukemia. 2019;34:957–62.

    Article  Google Scholar 

  10. Paul BS, Singh G, Bansal RK, Singla M. Isaac’s syndrome associated with myasthenia gravis and thymoma. Indian J Med Sci. 2010;64:320–24.

    Article  Google Scholar 

  11. Bailey RO, Dunn HG, Rubin AM, Ritaccio AL. Myasthenia gravis with thymoma and pure red blood cell aplasia. Am J Clin Pathol. 1988;89:687–93.

    Article  CAS  Google Scholar 

  12. Okui M, Yamamichi T, Asakawa A, Harada M, Horio H. Pure red cell aplasia associated with Good syndrome. Korean J Thorac Cardiovasc Surg. 2017;50:119–22.

    Article  Google Scholar 

  13. Kawakami T, Sekiguchi N, Kobayashi J, Imi T, Matsuda K, Yamane T, et al. Frequent STAT3 mutations in CD8+ T cells from patients with pure red cell aplasia. Blood Adv. 2018;2:2704–12.

    Article  CAS  Google Scholar 

  14. Motegi S, Uchiyama A, Yamada K, Toki S, Amano H, Ishikawa O. Lichen planus complicated with thymoma: report of three Japanese cases and review of the published work. J Dermatol. 2015;42:1072–77.

    Article  Google Scholar 

  15. Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmaki H, Andersson EI, et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med. 2012;366:1905–13.

    Article  CAS  Google Scholar 

  16. Tarr PE, Sneller MC, Mechanic LJ, Economides A, Eger CM, Strober W, et al. Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature. Med (Baltim). 2001;80:123–33.

    Article  CAS  Google Scholar 

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Acknowledgements

Henry and Marilyn Taub Foundation research grant (to JPM), R01HL118281, R01HL123904, R01HL132071, R35HL135795 (to JPM); and Vera and Joseph Dresner Foundation MDS Research Fund (to VV) and American Italian Cancer Foundation (to CG).

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  1. These authors contributed equally: Carmelo Gurnari, Jibran Durrani

Authors and Affiliations

  1. Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, OH, USA

    Carmelo Gurnari, Jibran Durrani, Simona Pagliuca, Ashwin Kishtagari, Hassan Awada, Cassandra M. Kerr, Vera Adema, Sunisa Kongkiatkamon, Alan E. Lichtin, Bhumika J. Patel, Valeria Visconte, Mikkael A. Sekeres & Jaroslaw P. Maciejewski

  2. Department of Biomedicine and Prevention, Phd in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome Tor Vergata, Rome, Italy

    Carmelo Gurnari

  3. Leukemia Program, Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland, OH, USA

    Alan E. Lichtin, Bhumika J. Patel, Mikkael A. Sekeres & Jaroslaw P. Maciejewski

  4. Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA

    James R. Cook

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  1. Carmelo Gurnari
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Contributions

CG and JD analyzed and interpreted the data and wrote the manuscript. AK and SP performed statistical analyses. HA, VA, CMK, VV, SK, and JRC helped in generating data and took part in samples’ selection. AL and BJP helped collecting patients’ samples. MAS reviewed the manuscript and provided important feedback on the manuscript. JPM conceived the idea, designed the study, collected clinical samples, and wrote the manuscript. All co‐authors edited and approved the paper.

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Correspondence to Jaroslaw P. Maciejewski.

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Gurnari, C., Durrani, J., Pagliuca, S. et al. Novel invariant features of Good syndrome. Leukemia 35, 1792–1796 (2021). https://doi.org/10.1038/s41375-020-01114-z

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