|Year : 2021 | Volume
| Issue : 2 | Page : 105-106
Thymoma-associated graft-versus-host disease-like erythroderma: A harbinger of poor prognosis
Chia-Hsien Yen1, Jui Lan2, Chao-Kai Hsu3, Julia Yu-Yun Lee3, Yi-Chien Yang1
1 Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
2 Department of Anatomic Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
3 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
|Date of Submission||17-Jul-2020|
|Date of Decision||03-Jan-2021|
|Date of Acceptance||21-Jan-2021|
|Date of Web Publication||23-Jun-2021|
Dr. Yi-Chien Yang
No. 123, Dapi Road. Niaosong Dist., Kaohsiung City 83301
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Yen CH, Lan J, Hsu CK, Lee JY, Yang YC. Thymoma-associated graft-versus-host disease-like erythroderma: A harbinger of poor prognosis. Dermatol Sin 2021;39:105-6
|How to cite this URL:|
Yen CH, Lan J, Hsu CK, Lee JY, Yang YC. Thymoma-associated graft-versus-host disease-like erythroderma: A harbinger of poor prognosis. Dermatol Sin [serial online] 2021 [cited 2022 Sep 26];39:105-6. Available from: https://www.dermsinica.org/text.asp?2021/39/2/105/319149
Thymomas originate from the epithelial cells of the thymus and account for 50% of the anterior mediastinal tumors. Thymomas are known to be associated with various paraneoplastic autoimmune diseases, including myasthenia gravis, pure red cell aplasia, and acquired hypogammaglobulinemia. Thymoma-associated graft-versus-host disease (GVHD)-like erythroderma is a rare paraneoplastic disorder.
A 51-year-old man was admitted to our hospital because of generalized muscle weakness with respiratory failure. Five years prior to this admission, his chest X-ray revealed pleural effusion with right hilum enlargement [Figure 1]a, and computer tomography (CT) showed an anterior mediastinal mass [Figure 1]b. The diagnosis of thymoma with pleural invasion was confirmed by CT-guided biopsy (WHO type B3, Masaoka stage IVa). Surgical intervention was not appropriate due to the advanced stage of the disease, so he received chemotherapy and radiotherapy. However, evidence of bone and liver metastases was found in subsequent imaging studies despite treatment.
|Figure 1: A 51-year-old Taiwanese man with invasive thymoma for 5 years developing GVHD-like erythroderma. (a) Chest X-ray showed pleural effusion and right hilum enlargement. (b) Computed tomography showed an anterior mediastinal tumor next to the ascending aorta with calcification (yellow arrow). (c-e) Generalized confluent scaly erythematous papules and plaques on his trunk and limbs including soles, involving more than 90% of the body surface area. Some lesions showed an annular pattern, and some had purpuric centers. Histopathological findings of the skin biopsy showed (f) confluent parakeratosis, focal vacuolar interface change with scattered necrotic keratinocytes mostly in the upper layer of epidermis with adjacent one or more lymphocytes (black arrows), and mild superficial perivascular inflammatory infiltrates (H and E, ×400). (g) CD4+ T-cells infiltration mostly in the papillary dermis (CD4, ×200); and (h) epidermal infiltration of CD8+ T-cells (CD8, ×200).|
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Upon this admission, he presented with widespread itchy skin lesions with other constitutional symptoms. There was no new medication during the past 3 months. Physical examination showed generalized confluent scaly erythematous papules and plaques on his scalp, face, trunk, and all limbs including palms and soles, which involved more than 90% of the body surface area [Figure 1]c, [Figure 1]d, [Figure 1]e without mucosal involvement. Skin biopsy revealed parakeratosis, basal cell vacuolization, dyskeratotic keratinocytes predominantly in the upper epidermis, exocytosis of lymphocytes, and a mild superficial perivascular inflammatory infiltrate [Figure 1]f. Immunohistochemical staining revealed the presence of CD4+ T-cells mostly in the papillary dermis [Figure 1]g, epidermal infiltration of CD8+ T-cells [Figure 1]h with reduced CD1a+ Langerhans cells [Supplementary Figure 1]a, and absence of CD123+ plasmacytoid dendritic cells (PDCs) [Supplementary Figure 1]b. These pathologic findings were reminiscent of those in GVHD. However, the patient never received blood transfusion, solid organ transplantation, or hematopoietic stem cell transplantation. Based on these findings, the diagnosis of thymoma-related GVHD-like erythroderma was made. The skin eruption, myasthenic crisis, and pneumonia developed almost simultaneously. High-potency topical glucocorticoids were attempted in our patient but failed to achieve any clinical improvement. Despite intensive antibiotic therapy, the patient eventually died of severe sepsis and multiple organ failure 4 months after developing erythroderma.
Thymoma-associated multiorgan autoimmunity (TAMA), first proposed by Wadhera et al. in 2007, is an autoinflammatory disorder of the liver, intestines, and skin, mimicking GVHD histopathologically in the setting of thymoma without hematopoietic stem cell transplantation. The thymus is where T cell development normally takes place through processes of positive and negative selections. These processes ensure that T cells leaving the thymus express receptors that are major histocompatibility complex-restricted but tolerant to self-antigens. In thymomas, negative selection is often compromised with abnormalities such as decreased autoimmune regulator gene expression, resulting in the production of autoreactive T-cells, which in combination with lower levels of peripheral and thymocytic regulatory T-cells may explain the pathologic mechanism of TAMA.
Skin is the most commonly affected organ in TAMA, manifesting various eruptions such as confluent scaly papules and plaques, morbilliform rash, erythroderma, and mucosal erosions. The histopathologic findings of GVHD-like erythroderma were consistent with classic GVHD, featuring parakeratosis, dyskeratotic keratinocytes, satellite cell necrosis, interface and perivascular dermatitis, and liquefaction degeneration. In our patient, the necrotic keratinocytes are mostly located in the upper layer of the epidermis, similar to those reported previously., Immunohistochemical findings include epidermal infiltration of more CD8+ than CD4+ T-cells and decreased numbers of CD1a+ Langerhans cells. CD123+ PDCs play an important role in the development of gastrointestinal acute GVHD, and thus, their presence facilitates the diagnosis of the disease., However, the presence of CD123+ PDCs was not found in our case. Whether GVHD and TAMA share a common CD123+ PDCs-related pathway remains unclear.
Currently, no consensus has been established for the treatment of thymoma-associated GVHD-like erythroderma, but several options have been considered effective, such as treatment of the underlying thymoma, topical or systemic glucocorticoids, narrow-band UVB phototherapy, cyclosporine, and intravenous immunoglobulin. Complete resection of the thymoma may be the best therapeutic option but is not always possible because of advanced disease stages. Unresectable thymoma with GVHD-like erythroderma portends a poor prognosis due to increased risks of infection and sepsis-related mortality. Chemotherapy in combination with prophylactic systemic antibiotics was thus proposed for patients with thymoma-associated GVHD-like erythroderma who could not otherwise receive surgical resection. Our patient failed to respond to high-potency topical glucocorticoids. However, other treatment options were not adopted because of various reasons, such as concurrent severe sepsis and inability to stand unassisted and financial difficulties. Despite treatment, 80% of the cases with cutaneous TAMA manifestations resulted in a fatal course, with most patients dying within 1 year.
To sum up, herein, we report a case of thymoma-associated GVHD-like erythroderma. The patient died of sepsis 4 months after the diagnosis of TAMA was made. The disease histopathologically mimics classic GVHD, but dyskeratotic keratinocytes are mostly distributed in the upper epidermis and clinically serves as a harbinger of a fatal prognosis.
This study was approved by Chang Gung Medical Foundation Institutional Review Board, IRB approval number 202000242B0 obtained on Feb. 25th, 2020. The informed patient consent was waived by the IRB.
Financial support and sponsorship
Conflicts of interest
Dr. Chao-Kai Hsu and Dr. Julia Yu-Yun Lee, editorial board members at Dermatologica Sinica, had no roles in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
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