Histopathological risk factors for malignancy in dermatomyositis.

AIMS: To identify possible histopathological risk factors for malignancy in skin biopsies of dermatomyositis patients. METHODS AND RESULTS: We analysed clinical metadata and studied 30 skin biopsies of 11 patients with and 12 patients without associated malignancy, who were treated in one secondary and one tertiary German medical centre between 2009 and 2022 and fulfilling the EULAR/ACR classification criteria for dermatomyositis. Specimens were categorized by malignancy status and evaluated based on haematoxylin and eosin (H&E), periodic acid Schiff (PAS), Alcian Blue, and anti-CD123 immunohistochemistry stains. After correcting for multiple testing, biopsies of patients with cancer exhibited more severe basement membrane thickening (P < 0.05) and pigment incontinence (P < 0.05) compared to patients without tumour burden. Patients with numerous subepidermal melanophages had a more than 5-times increased odds ratio to suffer from an internal malignancy (odds ratio [OR] 5.3, 95% confidence interval [CI] 1.3-54.2, P < 0.05). Furthermore, specimens of the malignancy group presented a distinct superficial distribution pattern of CD123+ plasmacytoid dendritic cells (PDCs, P < 0.01). Extravascular eosinophils were absent in all cases. CONCLUSION: Severity of basement membrane thickening, extent of pigment incontinence, and superficial distribution pattern of CD123+ PDCs could serve as useful histopathological indicators of risk for malignancy in dermatomyositis.

Immunomodulator Galectin-9 is Increased in Blood and Skin of Patients with Bullous Pemphigoid.

Massive recruitment of eosinophils into the dermis is a hallmark of bullous pemphigoid pathogenesis. Identifying the chemoattractant(s) guiding eosinophils into the skin in bullous pemphigoid is a prerequisite to thera-peutic targeting of eosinophil recruitment. Galectin -9 is a potent chemoattractant for eosinophils, but its potential role in bullous pemphigoid is unknown. The aim of this study was to determine the expression levels of galectin-9 in serum and skin of patients with bullous pemphigoid. Galectin-9 levels were significantly elevated in serum of patients with bullous pemphigoid compared with age- and sex-matched controls, but did not correlate with disease activity assessed with the Bullous Pemphigoid Disease Area Index. Galectin-9 expression was also increased in lesional skin of patients with bullous pemphigoid, and was expressed predominantly in eosinophils, neutrophils and keratinocytes. In conclusion, these results support the notion that galectin-9 may play a role in the patho-genesis of bullous pemphigoid.

Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence.

Primary melanomas >1 mm thickness are potentially curable by resection, but can recur metastatically. We assessed the prognostic value of T cell fraction (TCFr) and repertoire T cell clonality, measured by high-throughput-sequencing of the T cell receptor beta chain (TRB) in T2-T4 primary melanomas (n=199). TCFr accurately predicted progression-free survival (PFS) and was independent of thickness, ulceration, mitotic rate, or age. TCFr was second only to tumor thickness in its predictive value, using a gradient boosted model. For accurate PFS prediction, adding TCFr to tumor thickness was superior to adding any other histopathological variable. Furthermore, a TCFr >20% was protective regardless of tumor ulceration status, mitotic rate or presence of nodal disease. TCFr is a quantitative molecular assessment that predicts metastatic recurrence in primary melanoma patients whose disease has been resected surgically. This study suggests that a successful T cell-mediated antitumor response can be present in primary melanomas.