Thymoma followed by paroxysmal nocturnal hemoglobinuria: A unique clinical association in the context of multiorgan autoimmunity with a potential role for CD8+ T lymphocytes

Palmieri, Giovannella; Selleri, Carmine; Montella, Liliana; Bulgarelli, G C; Vitiello, Laura; Merkabaoui, Ghassan; Ricci, Patrizia; Vecchio, Luigi Del; Masci, Anna Maria; Means, Anthony; Rotoli, Bruno

doi:10.1002/ajh.20699

Cited by 16 publications

(8 citation statements)

References 9 publications

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“…The most common disorders affecting bone marrow precursors are pure red cell aplasia (PRCA) and ‘pure B cell aplasia’ (Good’s syndrome: thymoma and hypogammaglobulinaemia) (3–4% of patients). A few patients have also been described with agranulocytosis, myelodysplasia or paroxysmal nocturnal haemoglobinuria . The pathogenesis of these complications is thought to involve either the production of autoantibodies, e.g.…”

Section: Introductionmentioning

confidence: 99%

Clinical and laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma and hypogammaglobulinaemia)

Zaman

Huissoon

Buckland

et al. 2018

Clinical and Experimental Immunology

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Good's syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren's syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good's syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia.

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Section: Introductionmentioning

confidence: 99%

Clinical and laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma and hypogammaglobulinaemia)

Zaman

Huissoon

Buckland

et al. 2018

Clinical and Experimental Immunology

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“…Palmieri et al reported on the occurrence of paroxysmal nocturnal haemoglobinuria in a thymoma patient seven years after thymectomy. Causatively, they were able to attribute the reduction of circulating erythroid and myeloid progenitors to altered CD8+ T cells in this patient (126).…”

Section: Paroxysmal Nocturnal Haemoglobinuriamentioning

confidence: 73%

Autoimmune disorders and paraneoplastic syndromes in thymoma

Blum¹,

Misch²,

Kollmeier³

et al. 2020

J Thorac Dis

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Thymomas are counted among the rare tumour entities which are associated with autoimmune disorders (AIDs) and paraneoplastic syndromes (PNS) far more often than other malignancies. Through its complex immunological function in the context of the selection and maturation of T cells, the thymus is at the same time highly susceptible to disruptive factors caused by the development and growth of thymic tumours. These T cells, which are thought to develop to competent immune cells in the thymus, can instead adopt autoreactive behaviour due to the uncontrolled interplay of thymomas and become the trigger for AID or PNS affecting numerous organs and tissues within the human body. While myasthenia gravis is the most prevalent PNS in thymoma, numerous others have been described, be they related to neurological, cardiovascular, gastrointestinal, haematological, dermatological, endocrine or systemic disorders. This review article sheds light on the pathophysiology, epidemiology, specific clinical features and therapeutic options of the various forms as well as courses and outcomes of AID/PNS in association with thymomas.Whenever suitable and backed by the limited available evidence, the perspectives from both the thymoma and the affected organ/tissue will be highlighted. Specific issues addressed are the prognostic significance of thymectomy on myasthenia gravis and other thymoma-associated AID/PND and further the impact and safety of immunotherapies on AID and PND relating to thymomas.

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“…One proposed pathogenesis in MDS is autoantibodies that directly reject against hematopoietic cells, which was supported by the similar immune dysregulation of CD4 and CD8 T cells found in Good's syndrome [11,12]. In addition, CD8 T cells are proved to be involved in damaging hematopoietic precursors [6]. In the National Comprehensive Cancer Network guidelines of MDS, immunosuppressive treatments are reasonable choices in patients with MDS and hypocellular bone marrow, HLA‐DR15, and positive clones of PNH or young individuals at low‐ to intermediate‐risk.…”

Section: Discussionmentioning

confidence: 89%

“…Due to the dysfunction of both B and T lymphocytes, patients with Good's syndrome are more vulnerable to various pathogens, such as encapsulated bacteria, virus, fungus, and opportunistic infections. In addition to myasthenia gravis and Good's syndrome, paraneoplastic syndromes associated with thymoma (parathymic syndromes) could also present with autoimmune‐mediated hematological disorders, such as pure red cell aplasia, aplastic anemia, agranulocytosis, hemolytic anemia, pernicious anemia, and paroxysmal nocturnal hemoglobinuria [1–6]. Furthermore, myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more lineages, and ineffective hematopoiesis, and is associated with a variable risk of transformation to acute leukemia.…”

Section: Introductionmentioning

confidence: 99%

Myelodysplasia followed by Good's Syndrome: A unique manifestation associated with thymoma

Chen

Tsai

Lai

et al. 2012

The Kaohsiung J of Med Scie

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Good's syndrome, also known as thymoma with combined immunodeficiency, is rare. The immunodeficiency may precede, arise concurrently with or follow the diagnosis of thymoma. In addition to myasthenia gravis and Good's syndrome, paraneoplastic syndromes associated with thymoma can also be manifested with hematological disorders, such as pure red cell aplasia, aplastic anemia, agranulocytosis, hemolytic anemia, pernicious anemia, and paroxysmal nocturnal hemoglobinuria. Myelodysplastic syndrome is a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more lineages, ineffective hematopoiesis, and potential precursors of acute leukemia. One proposed pathogenesis of myelodysplasia is autoantibodies that directly reject against hematopoietic cells, but this situation is rare in thymoma. Herein, we report a thymoma patient with unique paraneoplastic syndromes who developed myelodysplasia prior to Good's syndrome. Early and accurate diagnosis of myelodysplastic syndrome is important for disease management, especially in patients whose myelodysplastic syndrome is possibly derived from autoimmunity. For thymoma patients with recurrent infections, comprehensive immunologic studies to exclude the possibility of Good's syndrome and prophylactic intravenous immunoglobulin infusion in suitable candidates are warranted.

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Thymoma followed by paroxysmal nocturnal hemoglobinuria: A unique clinical association in the context of multiorgan autoimmunity with a potential role for CD8+ T lymphocytes

Cited by 16 publications

References 9 publications

Clinical and laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma and hypogammaglobulinaemia)

Clinical and laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma and hypogammaglobulinaemia)

Autoimmune disorders and paraneoplastic syndromes in thymoma

Myelodysplasia followed by Good's Syndrome: A unique manifestation associated with thymoma

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