10.5826/dpc.1204a206
text/xml
2160-9381
2378
en
Stefano Caccavale
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
thymoma
Dermatologic Manifestations of Thymoma-associated Multiorgan Autoimmunity (TAMA) Syndrome: Cutaneous Signs of an Immune Dysregulation
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2022-10-31
2022-02-13
2022-10-31
2022-12-05
e2022206
Dermatol Pract Concept
Stefano Caccavale
2022/10/31
10.5826/dpc.1204a206
e2022206
Department of Dermatology, “Luigi Vanvitelli” University of Naples, Italy
2160-9381
thymoma
en
e2022206
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 Jul 26;33(2):250-257.
Dermatologic Manifestations of Thymoma-associated Multiorgan Autoimmunity (TAMA) Syndrome: Cutaneous Signs of an Immune Dysregulation
https://dpcj.org/index.php/dpc/article/download/2378/1796
            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                                                             eruption involving most of his face, trunk, bilateral upper
                                                                         and lower extremities. His palms and soles presented conflu-
Thymoma-associated multiorgan autoimmunity (TAMA)                        ent pink tender papules. Moreover, multiple chronic painful
syndrome is the consequence of auto-reactive T-cells activa-             erosions affected the oral mucosa (Figure 1). The patient re-
tion developing in the setting of a thymoma, which mediates              ported general malaise with deep asthenia and an abundant
graft-versus-host-disease (GHVD)-like reactions in several               chronic diarrhea.
tissues, including skin [1].                                                   A skin biopsy was performed and histologic examina-
                                                                         tion revealed an interface and perivascular dermatitis in
                                                                         the dermis. Epidermis showed psoriasiform hyperplasia,
Case Presentation
                                                                         diffuse parakeratosis and spongiosis, hypogranulosis, ne-
A 61-year-old man was admitted in our Dermatology                        crotic keratinocytes with intense eosinophilic cytoplasm
­Department for a skin rash appearing concomitantly to a                 (Figure 2). Although several differential diagnoses (includ-
nodal relapse of a malignant thymoma. Cutaneous examina-                 ing drug reaction, viral exanthema, pityriasis lichenoid, and
tion revealed a confluent erythematous and papulo-squamous               sub-erytrodermic psoriasis) were considered, relying on



Research Letter | Dermatol Pract Concept. 2022;12(4):e2022206                                                                           1
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                 In addition, our patient developed a progressive muscle
occurring in the setting of a malignant thymoma was finally           weakness. A thymoma-related myasthenia gravis was diag-
diagnosed.                                                            nosed after the detection of autoantibodies directed against



2                                                                         Research Letter | Dermatol Pract Concept. 2022;12(4):e2022206
acetylcholine receptor and electrophysiological evaluation of     reported in literature to date. The dermatologic manifesta-
neuromuscular junctions.                                          tions of TAMA syndrome consist of diffuse papulo-squamous
    After three months our patient died as a result of the        rash, often involving palms and soles, with possible lesions
rapidly progressive clinical deterioration and the hypoxemic      of oral mucosa. TAMA syndrome should be always kept in
respiratory failure consequent to a lung infection and myas-      mind on a thymoma background when these specific skin
thenia gravis.                                                    signs are associated with systemic manifestations, first of all
    Myasthenia gravis is the most typical paraneoplastic syn-     diarrhea.
drome associated with thymoma; it does not always develop
at diagnosis, but it has a high impact of morbidity and mor-
                                                                  References
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causes of a real GHVD, such as hematopoietic stem cell             2. Tian W, Li X, Sun Y, Wang J, Jiang G, Tong H. Myasthenia gravis
transplantation (HSCT) and transfusion of non-irradiated              affects overall survival in patients with thymoma: an analysis of
blood. Being not associated to HSCT, Waldhera et al decided           multicentre database using propensity score matching. Interact
to collect the GVHD-like reactions occurred in the setting of         Cardiovasc Thorac Surg. 2021;33(2):250-257. DOI: 10.1093/
                                                                      icvts/ivab074. PMID: 34151968. PMCID: PMC8691723.
a thymoma under the umbrella name of TAMA syndrome
                                                                   3. Holder J, North J, Bourke J, Colloby P, Fletcher A, Graham-Brown
[1]. First described cases were characterized by a constant
                                                                      R, Whaley K. Thymoma-associated cutaneous graft-versus-host-
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tected in multiple organs, including not only gastrointestinal        9604457.
tract, but also skin, thyroid and liver [4].                       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
Conclusions                                                           Pathol. 2015;42(10):663-668. DOI: 10.1111/cup.12642. PMID:
                                                                      26509934. PMCID: PMC5072282.
We remark the uniqueness and interest of this case, since
TAMA syndrome is a very rare disorder and with few cases




Research Letter | Dermatol Pract Concept. 2022;12(4):e2022206                                                                        3
