Thymoma-associated Multiorgan Autoimmunity Research Articles

DP21 Thymoma and the skin: manifestations of multiorgan autoimmunity

Abstract We present three patients who developed distinct cutaneous manifestations of thymoma: a rare mediastinal tumour. A 25-year-old man was treated for myasthenic crisis. Past medical history included thymectomy in 2016. Admission imaging confirmed recurrence of thymoma. He developed a red–brown macular rash affecting the trunk, back and thighs. Biopsy showed a florid lichenoid dermatitis consistent with graft-versus-host disease (GVHD). After resolution with steroids and mycophenolate mofetil, he subsequently developed a Stevens–Johnson syndrome/toxic epidermal necrolysis-like eruption with erythroderma and epidermal loss. Unfortunately, he developed multiorgan failure and died shortly afterward. A 43-year-old man presented to the emergency dermatology clinic with a 4-month history of a blistering rash affecting the chest and limbs. His previous medical history was significant for thymoma in 2008 and a recurrence in 2013. Skin biopsy demonstrated changes suggestive of bullous pemphigoid, and repeat computed tomography confirmed the recurrence of thymoma. Enzyme-linked immunosorbent assay testing was positive for bullous pemphigoid 180. He has responded well to prednisolone and doxycycline. A 51-year-old woman was reviewed in 2020 and 2021 with pruritic hyperpigmented patches affecting the face, trunk and limbs. Her past medical history included several relapses of thymoma with occurrence in 2002 and relapses in 2007, 2008, 2011, 2015 and 2021. Skin biopsy in June 2021 showed features of cutaneous GVHD. She received ruxolitinib and tapering steroids for thymoma-associated multiorgan autoimmunity (TAMA)-like GVHD and has had a remarkable improvement in her skin disease. Thymoma is described as a rare neoplasm, and up to 34% of thymomas are thought to be accompanied by symptoms of autoimmunity. The most frequently described syndromes include myasthenia gravis, pure red blood cell aplasia and hypogammaglobulinaemia. Other reported presentations include panencephalitis, enterocolitis and autoimmune hepatitis. Thymoma and cutaneous autoimmune presentations have been previously described, often in association with two rare syndromes: TAMA and paraneoplastic autoimmune multiorgan syndrome (PAMS). Both conditions demonstrate variability in clinical phenotype, driven by the activation of humoral and cellular immune responses. Clinically, patients may present with a spectrum of skin disease, including GVHD-like exanthems, lichen planus-like disease and pemphigus-like and pemphigoid-like lesions. Our case series demonstrates the heterogeneous cutaneous manifestations of thymoma-induced autoimmunity. We also describe two extremely rare phenomena accompanying thymomas: TAMA and PAMS. We also suggest that there is much crossover between these syndromes and previous definitions may require further review. This case series also highlights the importance of the wider multidisciplinary team in managing these patients and the complexities of their disease.

RARE PRESENTATION OF A THYMOMA AT AN INFREQUENT LOCATION

RARE PRESENTATION OF A THYMOMA AT AN INFREQUENT LOCATION

A case of thymoma-associated multiorgan autoimmunity including polymyositis and myocarditis

BackgroundPolymyositis and myocarditis associated with thymoma are exceptionally rare conditions and usually accompanied by myasthenia gravis (MG) and have been recognized as critical conditions. Thymoma-associated multiorgan autoimmunity was reported recently with skin, liver, and intestinal manifestations similar to those seen in graft-versus-host disease.Case presentationA 77-year-old female presented to our department with exacerbation of ptosis and local recurrence of thymoma. Chest computed tomography revealed local recurrence of thymoma. Following 6 month observation, erythema on the extremities and body trunk suddenly appeared. Afterwards, the patient developed progressive muscle weakness and fatigue. We diagnosed as myocarditis and polymyositis. She was transferred to the intensive-care unit and received artificial ventilation. Steroid pulse therapy was induced immediately. The blood test findings were markedly improved, but the symptoms of MG and weakness of the muscles persisted. Various treatment including eculizumab was induced, and the symptoms of MG and weakness of the muscles were improved. On the 136th day of hospitalization, she was discharged.ConclusionWe were able to cure this patient, as we were able to start treatment immediately after the appearance of severe symptoms. An early diagnosis and treatment are important for curing such patients.

Thymoma-associated multiorgan autoimmunity with cutaneous only presentation: A case report.

Thymoma-associated multiorgan autoimmunity disease can be seen in patients with thymomas and presents with features of graft versus host disease. Here, we report a case of a 52-year-old woman with a complex medical history including malignant thymoma, myasthenia gravis, Good’s syndrome, and T cell large granular lymphocytic leukemia who presented with a diffuse pruritic rash ultimately found to be compatible with a cutaneous presentation of thymoma-associated multiorgan autoimmunity disease. The eruption heralded the recurrence of the malignant thymoma and the rash was ultimately found to be resistant to a multitude of therapies except for oral corticosteroids.

16796 Graft-versus-host disease–like erythroderma associated with aggravation of thymoma

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare paraneoplastic disease defined as thymoma with liver, intestine or skin manifestations, which resembles graft-versus-host disease (GVHD) histopathologically in the absence of hematopoietic stem cell transplantation. A 76-year-old woman who had been diagnosed with invasive thymoma presented with scaly erythema and reddish papules across the trunk. She had been admitted to internal medicine because of febrile sensation and general fatigue suspecting meningitis. The initial differential diagnosis for her cutaneous lesions included drug eruption due to antibiotics and viral exanthem. Antibiotics were stopped and she was treated with topical steroid, oral antihistamine. But there was no effect on skin lesion, which then spread rapidly to the whole body. And she died of aggravation of thymoma a few days later. The pathologic findings of a biopsy specimen from the abdomen revealed parakeratosis, many apoptotic cells in the epidermal layer, perivascular and interface dermatitis with lymphocytic infiltration. Theses pathologic findings were similar to those seen in GVHD. Interestingly, she never underwent allogenic stem cell or solid-organ transplantation. Given the presence of GVHD-like skin symptoms and aggravation of thymoma, the diagnosis of thymoma associated GVHD-like erythroderma, one of the findings in thymoma-associated multiorgan autoimmunity, was made.

Thymoma-associated multi-organ autoimmunity: A case of graft-versus-host disease-like erythroderma complicated by Good syndrome successfully treated by thymectomy.

Thymoma-associated multi-organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft-versus-host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD-like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD-like erythroderma.

Diminished regulatory T cells in cutaneous lesions of thymoma-associated multi-organ autoimmunity: a newly described paraneoplastic autoimmune disorder with fatal clinical course

Thymoma-associated multi-organ autoimmunity is a rare, autoimmune disease that causes colitis, liver dysfunction and cutaneous graft-versus-host (GVH)-like skin damage. This paraneoplastic autoimmune disorder may be due to inadequate T cell selection in the tumour environment of the thymus. Although sporadic case reports have revealed its clinical features, little is known about its pathological mechanism. By comparing the skin-infiltrating T cell subsets with those of GVH disease (GVHD) and other inflammatory skin diseases, we sought to elucidate the pathological mechanism of thymoma-associated multi-organ autoimmunity. Histopathological and immunohistochemical analysis of skin biopsies was performed for three patients with thymoma-associated multi-organ autoimmunity. Histopathological findings of thymoma-associated multi-organ autoimmunity were indistinguishable from those of patients with acute GVHD, although the aetiologies of these diseases are completely different. The frequency of regulatory T cells (T(regs)) is reduced in cutaneous lesions and CD8+ cytotoxic T lymphocytes that massively infiltrate into the epidermis of patients with thymoma-associated multi-organ autoimmunity. Additionally, the ratio of T helper type 17 (Th17) cells to CD4+ cells in patients with thymoma-associated multi-organ autoimmunity and acute GVHD was higher than that in healthy controls, but similar to that in psoriasis vulgaris patients. Similarity of the skin-infiltrating T cell subsets with those of acute GVHD suggested that skin damage in patients with thymoma-associated multi-organ autoimmunity might be induced by self-reactive cytotoxic T lymphocytes under the diminished suppressive capacity of T(regs).

The Etiology of Paraneoplastic Autoimmunity

Although they may sometimes appear similar, paraneoplastic autoimmunity has a unique pathogenesis, different from the classical autoimmune diseases not associated with cancer. When distinguished clinically, paraneoplastic autoimmunity is more severe and often presents with a broader range of clinical signs and symptoms. Management of these patients is difficult and is usually centered in part on treatment of the underlying malignancy. Self-antigens recognized in the setting of paraneoplastic autoimmunity can be diverse, and the number of determinants recognized within a single antigen can be numerous. This review uses prototypic examples of paraneoplastic immune-mediated diseases and their associated malignancies to describe the mechanisms by which immune dysregulation can occur in the setting of cancer. Specific diseases covered include paraneoplastic pemphigus, Sweet's syndrome, pyoderma gangrenosum, thymoma-associated multiorgan autoimmunity, myasthenia gravis, autoimmune hemolytic anemia, immune thrombocytopenia, and the paraneoplastic neurological syndromes. The malignancies discussed include thymoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia, among others. The mechanisms by which cancers induce autoimmunity are broken down into the following categories: disruption of central tolerance, peripheral immune dysregulation, and alteration of self-antigens. For each category, examples of paraneoplastic autoimmune diseases and their associated malignancies are discussed. Finally, mechanisms by which cancer treatment can lead to autoimmunity and examples of polymorphisms that are linked to both cancer and autoimmunity are discussed.