Andrea P. Moy

Immunologic Overlap of Helper T-Cell Subtypes 17 and 22 in Erythrodermic Psoriasis and Atopic Dermatitis.

IMPORTANCE Psoriasis and atopic dermatitis (AD) are inflammatory diseases thought to be mediated by helper T-cell subtypes 1 and 2 (TH1 and TH2), respectively. Although psoriasis and AD show histopathologic differences during chronic disease, they are difficult to distinguish histologically during erythrodermic exacerbations. OBJECTIVE To determine whether the immune phenotype of helper T cells can differentiate erythrodermic psoriasis and erythrodermic AD by studying skin biopsy specimens of patients with psoriasis and AD during erythrodermic and chronic disease phases. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective study using biopsy samples of psoriasis, AD, and erythroderma belonging to the surgical pathology files of the James Homer Wright Pathology Laboratories, Massachusetts General Hospital, and collected from January 1, 2004, through December 31, 2011. Samples were obtained from patients with chronic psoriasis (n = 20), chronic AD (n = 20), erythroderma subsequently diagnosed as psoriasis (n = 7), and erythroderma subsequently diagnosed as AD (n = 5). We evaluated immunohistochemical stains for CD3 and dual stains for CD4 and T-bet, GATA binding protein 3 (GATA3), signal transducer and activator of transcription 3 (STAT3), or basonuclin 2 (BNC2), which are transcription factors reported to be specific and mutually exclusive for TH1, TH2, TH17, and TH22 cells, respectively. Two investigators independently counted CD3+ cells and dual-labeled CD4+/T-bet+, CD4+/GATA3+, CD4+/STAT3+, and CD4+/BNC2+ cells in 5 consecutive high-power fields. MAIN OUTCOMES AND MEASURES We evaluated the percentage of TH1, TH2, TH17, and TH22 cells in CD3+ T cells and the TH1:TH2 ratio in chronic psoriasis, chronic AD, erythrodermic psoriasis, and erythrodermic AD. RESULTS We found a significant difference in the TH1:TH2 ratio between chronic psoriasis and chronic AD (0.26 and 0.09, respectively; P = .005). However, we detected no significant difference in the percentage of TH1 (6.5% and 4.8%), TH2 (55.2% and 64.6%), TH17 (14.7% and 30.4%), and TH22 (3.8% and 3.3%) cells of CD3+ T cells or in the TH1:TH2 ratio (0.16 and 0.07) within biopsy specimens from patients with erythrodermic psoriasis and AD, respectively. CONCLUSIONS AND RELEVANCE This study confirms the TH1- and TH2-skewed phenotype of chronic psoriasis and chronic AD, respectively. However, the immune phenotype, as determined by immunohistochemical analysis, cannot discriminate between these inflammatory diseases in the erythrodermic phase. These findings advance our understanding of the pathophysiological characteristics of erythroderma, psoriasis, and AD and may influence therapeutic decisions.

Identification of a Th2- and Th17-skewed immune phenotype in chronic urticaria with Th22 reduction dependent on autoimmunity and thyroid disease markers.

Chronic urticaria is a condition with many inciting factors and often presents a therapeutic challenge to clinicians. In addition to a central role for mast cells, an immune dysregulated state related to cytokine/chemokine alterations is increasingly being recognized.

Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma.

Bile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well‐differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma.

Lymphatic invasion and angiotropism in primary cutaneous melanoma

Access of melanoma cells to the cutaneous vasculature either via lymphatic invasion or angiotropism is a proposed mechanism for metastasis. Lymphatic invasion is believed to be a mechanism by which melanoma cells can disseminate to regional lymph nodes and to distant sites and may be predictive of adverse outcomes. Although it can be detected on hematoxylin- and eosin-stained sections, sensitivity is markedly improved by immunohistochemistry for lymphatic endothelial cells. Multiple studies have reported a significant association between the presence of lymphatic invasion and sentinel lymph node metastasis and survival. More recently, extravascular migratory metastasis has been suggested as another means by which melanoma cells can spread. Angiotropism, the histopathologic correlate of extravascular migratory metastasis, has also been associated with melanoma metastasis and disease recurrence. Although lymphatic invasion and angiotropism are not currently part of routine melanoma reporting, the detection of these attributes using ancillary immunohistochemical stains may be useful in therapeutic planning for patients with melanoma.

Th1- and Th17-polarized immune infiltrates in eosinophilic fasciitis—A potential marker for histopathologic distinction from morphea

Morphea (localized scleroderma) and eosinophilic fasciitis (EF) are rare fibrosing disorders which may present a diagnostic challenge. While histopathologic features are often distinct, in some cases there may be overlap. T‐cells contribute to etiopathogenesis of both autoimmune conditions. We sought to determine whether T‐cell immune polarization enables histopathologic distinction.

Fetal-type gastrointestinal adenocarcinoma: a morphologically distinct entity with unfavourable prognosis

Aims This multi-institutional study and a re-evaluation of the TCGA cohort explores the morphological spectrum, genetics and outcome of GI (gastrointestinal) hepatoid tumours, tumours expressing alpha-fetoprotein (AFP) and fetal-type (FT) GI adenocarcinomas. Methods 44 tumours with evidence of hepatocellular differentiation were evaluated for morphology as well as by immunohistochemistry for AFP, HepPar1, glypican-3 and arginase-1 and by in situ hybridisation for albumin. Three categories were defined: type I (hepatoid: morphological evidence of hepatocellular differentiation), type II (FT GI adenocarcinoma: tubular profiles and subnuclear vacuolisation, resembling fetal intestine) and type III: positive for at least two hepatocyte-specific markers but lacking morphological evidence of hepatocellular differentiation. GI adenocarcinomas in the TCGA cohort were also evaluated (n=829). Results 18 cases were classified as type I, 19 as FT GI adenocarcinomas and 7 as type III (resembling conventional gastrointestinal carcinomas). Serum AFP was elevated in 92% of cases. 93% of tumours were positive for glypican-3, 90% for albumin and 89% for AFP. Arginase-1 was restricted to 35% of type 1 tumours. TCGA gastric tumours with elevated AFP expression showed morphological features of FT GI adenocarcinoma (70%) and were exclusively MSI stable. TCGA gastric adenocarcinomas with high AFP expression showed inferior survival on univariate and multivariate analysis. Conclusions FT GI adenocarcinomas show a distinctive morphological and immunohistochemical profile. Gastric adenocarcinomas with elevated expression of AFP morphologically resemble FT GI adenocarcinomas, demonstrate aggressive behaviour, independent of grade and stage, and a distinct genetic profile.

T‐helper immune phenotype may underlie ‘paradoxical’ tumour necrosis factor‐α inhibitor therapy‐related psoriasiform dermatitis

Therapeutics targeting tumour necrosis factor (TNF)‐α are effective for psoriasis; however, in patients treated for other disorders, psoriasis may worsen and psoriasiform dermatitis (PsoD) may arise. T helper (Th) cytokines in psoriasis upregulate keratin (K)17, which modulates TNF‐α transduction, leading to vascular adhesion molecule upregulation and lymphocytic extravasation.

Lymphatic invasion predicts sentinel lymph node metastasis and adverse outcome in primary cutaneous melanoma: MOYet al .

Sentinel lymph node (SLN) metastasis is a powerful predictor of survival in primary cutaneous melanoma. Lymphatic invasion (LI) may correlate with increased risk of SLN metastasis. Intralymphatic metastases, often difficult to detect on hematoxylin and eosin (H&E) stained sections, are readily identified with dual immunohistochemistry for melanocytic and lymphatic markers.