Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2022;12(4):e2022206 1 Dermatologic Manifestations of Thymoma-associated Multiorgan Autoimmunity (TAMA) Syndrome: Cutaneous Signs of an Immune Dysregulation Luigi Rossiello1, Amalia Lupoli2, Giuseppe Cicala1, Gianfranco De Dominicis3, Vittorio Tancredi2, Stefano Caccavale2 1 Department of Dermatology, A.O.R.N. “A. Cardarelli”, Naples, Italy. 2 Department of Dermatology, “Luigi Vanvitelli” University of Naples, Italy. 3 Department of Pathology, A.O.R.N. “A. Cardarelli”, Naples, Italy. Key words: TAMA syndrome, myastenia gravis, GVHD, thymoma Citation: Rossiello L, Lupoli A, Cicala G, De Dominicis G, Tancredi V, Caccavale S. Dermatologic manifestations of thymoma-associated multiorgan autoimmunity (TAMA) syndrome: cutaneous signs of an immune dysregulation. Dermatol Pract Concept. 2022;12(4):e2022206. DOI: https://doi.org/10.5826/dpc.1204a206 Accepted: February 25, 2022; Published: October 2022 Copyright: ©2022 Rossiello et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Vittorio Tancredi, MD, Dermatology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Via Sergio Pansini, 5, 80131 Naples, Italy; phone: +39 3313919797; fax: +39 0815468759; E-mail: tancredivittorio@ymail.com Introduction Thymoma-associated multiorgan autoimmunity (TAMA) syndrome is the consequence of auto-reactive T-cells activa- tion developing in the setting of a thymoma, which mediates graft-versus-host-disease (GHVD)-like reactions in several tissues, including skin [1]. Case Presentation A 61-year-old man was admitted in our Dermatology Department for a skin rash appearing concomitantly to a nodal relapse of a malignant thymoma. Cutaneous examina- tion revealed a confluent erythematous and papulo-squamous eruption involving most of his face, trunk, bilateral upper and lower extremities. His palms and soles presented conflu- ent pink tender papules. Moreover, multiple chronic painful erosions affected the oral mucosa (Figure 1). The patient re- ported general malaise with deep asthenia and an abundant chronic diarrhea. A skin biopsy was performed and histologic examina- tion revealed an interface and perivascular dermatitis in the dermis. Epidermis showed psoriasiform hyperplasia, diffuse parakeratosis and spongiosis, hypogranulosis, ne- crotic keratinocytes with intense eosinophilic cytoplasm (Figure 2). Although several differential diagnoses (includ- ing drug reaction, viral exanthema, pityriasis lichenoid, and sub-erytrodermic psoriasis) were considered, relying on 2 Research Letter | Dermatol Pract Concept. 2022;12(4):e2022206 Figure 1. Erythematous and scaly papulosquamous eruption. Figure 2. (A) Histology showing epidermal hyperplasia (H&E, 40X). Higher magnification highlights parakeratosis, epidermal spongiosi , hypogranulosis and some apoptotic keratinocytes characterized by intensely eosinophilic cytoplasm. (B) The underlying dermis contains few infiltrates of lymphocytes (H&E, 200X). anamnesis, histology and literature, a GVHD-like reaction occurring in the setting of a malignant thymoma was finally diagnosed. In addition, our patient developed a progressive muscle weakness. A thymoma-related myasthenia gravis was diag- nosed after the detection of autoantibodies directed against Research Letter | Dermatol Pract Concept. 2022;12(4):e2022206 3 acetylcholine receptor and electrophysiological evaluation of neuromuscular junctions. After three months our patient died as a result of the rapidly progressive clinical deterioration and the hypoxemic respiratory failure consequent to a lung infection and myas- thenia gravis. Myasthenia gravis is the most typical paraneoplastic syn- drome associated with thymoma; it does not always develop at diagnosis, but it has a high impact of morbidity and mor- tality [2]. GVHD-like reactions are rare immune response that occur particularly at level of skin, intestine, or liver, which resemble GVHD on histopathology, except for graft lympho- cytes [3]. The diagnosis requires the exclusion of the main causes of a real GHVD, such as hematopoietic stem cell transplantation (HSCT) and transfusion of non-irradiated blood. Being not associated to HSCT, Waldhera et al decided to collect the GVHD-like reactions occurred in the setting of a thymoma under the umbrella name of TAMA syndrome [1]. First described cases were characterized by a constant colon involvement; subsequently, TAMA reactions were de- tected in multiple organs, including not only gastrointestinal tract, but also skin, thyroid and liver [4]. Conclusions We remark the uniqueness and interest of this case, since TAMA syndrome is a very rare disorder and with few cases reported in literature to date. The dermatologic manifesta- tions of TAMA syndrome consist of diffuse papulo-squamous rash, often involving palms and soles, with possible lesions of oral mucosa. TAMA syndrome should be always kept in mind on a thymoma background when these specific skin signs are associated with systemic manifestations, first of all diarrhea. References 1. Waldhera A, Maverakis E, Mitisiades N, Lara PN, Fung MA, Lynch PJ. Thymoma associated multiorgan autoimmunity: a graft-versus-host-like-disease. J Am Acad Dematol. 2007; 57(4):683-689. DOI: 10.1016/j.jaad.2007.02.027. PMID: 17433850. 2. Tian W, Li X, Sun Y, Wang J, Jiang G, Tong H. Myasthenia gravis affects overall survival in patients with thymoma: an analysis of multicentre database using propensity score matching. Interact Cardiovasc Thorac Surg. 2021;33(2):250-257. DOI: 10.1093/ icvts/ivab074. PMID: 34151968. PMCID: PMC8691723. 3. Holder J, North J, Bourke J, Colloby P, Fletcher A, Graham-Brown R, Whaley K. Thymoma-associated cutaneous graft-versus-host- like reaction. Clin Exp Dermatol. 1997;22(6):287-290. PMID: 9604457. 4. Warren S, Nehal K, Querfeld C, Wong R, Huang J, Pulitzer M. Graft-versus-host disease-like erythroderma: a manifestation of thymoma-associated multiorgan autoimmunity. J Cutan Pathol. 2015;42(10):663-668. DOI: 10.1111/cup.12642. PMID: 26509934. PMCID: PMC5072282.