Cynthia M. Magro

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare paraneoplastic syndrome characterized by graft-versus-host disease (GVHD)–like manifestations. The disorder is thought to arise from a disruption to central immune tolerance of T cells secondary to neoplastic growth of thymic epithelial cells. Thymic epithelial cells are crucial in T-cell education: distinguishing between self-antigens and foreign antigens. This process relies on a protein, the autoimmune regulator (AIRE), which negatively selects and eliminates T cells that are self-reactive. With neoplastic transformation of thymic cells, these cells may exhibit reduced AIRE, leading to an overabundance of autoreactive T cells. These autoreactive T cells mediate the sequelae of the GVHD-like presentation, with skin, liver, and gastrointestinal tract manifestations. We describe a case of a 74-year-old patient with a medical history of thymoma and multiple autoimmune conditions, who presented for diffuse psoriasiform eruption of the trunk and back. Skin biopsy further revealed epidermal hyperplasia with interface change, extensive dyskeratosis, and numerous apoptotic keratinocytes within parakeratotic scale, including striking involvement of the follicular epithelium. Our patient developed hepatobiliary and cholestasis injury, with rising bilirubin, AST, and ALT levels. Despite therapeutic modifications, his cutaneous and systemic disease progressed, and he died approximately 1 month after the diagnosis of TAMA due to complications of small bowel obstruction. This case highlights the pressing need for heightened clinical suspicion and a multidisciplinary team approach when presented with a thymoma patient.

Programmed cell death-1 checkpoint inhibitors have significantly improved cancer survival outcomes. More than half of patients on programmed cell death-1 checkpoint inhibitors develop cutaneous immune-related complications. The prognostic significance of eruptions biopsied in routine clinical practice remains underexplored. We aimed to characterize biopsy-confirmed cutaneous toxicities associated with checkpoint inhibitors and assess their association with survival. We conducted a retrospective study of biopsy-confirmed checkpoint inhibitor–associated dermatoses at our single institution between September 2014 and June 2025, analyzing clinical features, histopathology, treatment outcomes, and progression-free (PFS) and overall survival. Seventy-five patients were included (mean age 67.0 years [24, 95]; 52% female). Most developed reactions within 6 months of initiating therapy. Most took pembrolizumab and nivolumab. Histopathologic categories included type IV hypersensitivity (T4HS) lichenoid (N = 29; 39%), T4HS eczematoid (N = 10; 13%), other T4HS patterns (N = 6; 8%) including 1 fatal case of toxic epidermal necrolysis, vesiculobullous (N = 12; 16%), psoriasis (N = 4; 5%), reversible epitheliotropic T-cell dyscrasia (N = 4; 5%), sclerodermoid (N = 4; 5%), Sweet syndrome (N = 3; 4%), and miscellaneous (N = 3; 4%). Most eruptions improved or remained stable with treatment with 1 fatal case of toxic epidermal necrolysis. Patients with T4HS-mediated reaction, 60% of our cohort, had reduced tumor progression hazard with longer PFS (hazard ratio = 0.49 [0.23–1.05], P = 0.07; PFS-p _adj = 0.06, PFS-late-weighted p _adj = 0.04). Overall survival did not differ. Our study is limited by sample size. Checkpoint inhibitor–associated dermatoses resemble established standard cutaneous adaptive B- and T-cell–driven dermatoses. Regulatory T-cell inhibition, allowing emergence of autoreactive B and T cells or unmasking of subclinical hypersensitivity, is likely pathogenetically key.

Persistent agmination of lymphomatoid papulosis (PALP) is a rare, anatomically localized variant of lymphomatoid papulosis (LYP) characterized by clustered papules superimposed on a chronic persistent patch or plaque which resembles cutaneous T-cell lymphoma. The histologic patterns may be variable, and differentiation from early-stage cutaneous T-cell lymphoma (CTCL), particularly unilesional mycosis fungoides (MF), can be challenging. We report an 18-year-old woman with a longstanding CD8-positive T-cell dyscrasia, initially diagnosed at age 10 as Type B LYP showing folliculocentricity. She experienced a recurrence at age 14, and 3 years later she developed a persistent, localized patch on the thigh with superimposed papules which exhibited a waxing and waning course. Histologic examination of both the persistent patch and episodic papular component revealed a very similar morphology which was the one manifesting an overlapping morphology of Type B LYP and pityriasis lichenoides chronica (PLC); there was follicular involvement similar to the earlier 2016 biopsy. PALP is a very rare variant of LYP with most of the reported cases describing the persistent patch as having features of cutaneous T-cell lymphoma, typically mycosis fungoides. We describe a patient with PALP where both the episodic papules and the persistent patch showed a similar histomorphology which in turn mirrored the previous pathology from 2016 that was characteristic for LYP clinically and was biopsy proven folliculotropic Type B LYP. Two other cases of PALP showing a persistent patch with classic features of LYP have been previously published. Hence, there is a subset of PALP where the persistent lesion is compatible with LYP as opposed to being one of lymphoma. The persistence of LYP challenges this conceptualization of LYP as a lymphoproliferative disorder where complete regression is a requisite.

Diffuse dermal angiomatosis represents a reactive form of microvascular proliferation characteristically linked with vascular insufficiency of diverse etiology. It occurs most commonly on the lower extremity where a frequent association is venous insufficiency; however, it can exhibit breast localization falling under the designation of diffuse dermal angiomatosis of the breast (DDAB). The clinical presentation of DDAB can be striking and resembles a catastrophic thrombogenic vasculopathy such as purpura fulminans, calciphylaxis, and antiphospholipid antibody syndrome. However, a less common presentation is one of diffuse erythema mimicking inflammatory breast carcinoma as the main clinical presentation. Most articles devoted to the topic of DDAB describe a reproducible association with diseases and/or other risk factors such as smoking that can result in microvascular insufficiency. In contradistinction, the development of this reactive vascular process in a healthy patient would be considered exceptionally uncommon, albeit it has been reported. We describe a case of bilateral DDAB in a patient who was 21 weeks pregnant; the clinical diagnosis was inflammatory breast carcinoma. The case was unusual for three primary reasons: the age of the patient, the lack of any history of vascular insufficiency, and the clinical presentation resembling inflammatory breast carcinoma. Although the downstream effects eventuated in dermal angiomatosis, the upstream mechanisms were clearly different than what is implicated in conventional DDAB. The pathophysiology as it applies to this case is explored. Our patient serves to expand the clinical and pathophysiologic spectrum of DDAB .

Primary cutaneous follicle center lymphoma rarely presents as macular alopecia and is typically characterized by solitary papules and nodules on the head, neck, and trunk. We report a 24-year-old woman with frontal alopecia that clinically resembled frontal fibrosing alopecia but was ultimately diagnosed as primary cutaneous follicle center lymphoma. The patient presented with pronounced alopecia over the left frontal scalp superimposed on milder bitemporal alopecia and intermittent symptoms of scalp irritation. Histopathologic examination of a scalp biopsy revealed a nodular lymphocytic infiltrate with irregular germinal centers localized to the adventitial dermis of the eccrine coil and the interadnexal interstitium. Immunophenotyping confirmed B-cell clonality, with findings consistent with primary cutaneous follicle center lymphoma. This case highlights the importance of biopsy in atypical alopecia presentations, as histologic findings were pivotal in diagnosing primary cutaneous follicle center lymphoma with concurrent frontal fibrosing alopecia features.