ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in three infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (seven and twelve from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated-ERK, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, while CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, ten with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis, and provides guidance for the clinical management of this emerging histiocytic entity.

YAP1-NUTM1 fusion transcripts have been recently reported in poroma and porocarcinoma. NUTM1 translocation can be screened by nuclear protein in testis (NUT) immunohistochemistry in various malignancies, but its diagnostic performance has not been thoroughly validated on a large cohort of cutaneous epithelial neoplasms. We have evaluated NUT immunohistochemical expression in a large cohort encompassing 835 cases of various cutaneous epidermal or adnexal epithelial neoplasms. NUT expression was specific to eccrine poromas and porocarcinoma, with 32% of cases showing NUT expression. All other cutaneous tumors tested lacked NUT expression, including mimickers such as seborrheic keratosis, Bowen disease, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, nodular hidradenoma, and all other adnexal tumors tested. Remarkably, NUT expression was more frequent in a distinct morphologic subgroup. Indeed, 93% of poroid hidradenoma (dermal/subcutaneous nodular poroma, 13/14) and 80% of poroid hidradenocarcinoma cases (malignant poroid hidradenoma, 4/5) showed NUT expression, in contrast to 17% and 11% of classic poroma (4/23) and porocarcinoma cases (4/35), respectively. RNA sequencing of 12 NUT-positive neoplasms further confirmed the presence of a YAP1-NUTM1 fusion transcript in all cases, and also an EMC7-NUTM1 gene fusion in a single case. In the setting of a cutaneous adnexal neoplasm, nuclear expression of NUT accurately and specifically diagnosed a specific subgroup of benign and malignant poroid tumors, all associated with a NUTM1 fusion, which frequently harbored a poroid hidradenoma morphology.

Clinical features and outcome are the most discriminative to differentiate the two entities. Even histological and molecular markers were not fully specific; abnormal vs. normal T-cell phenotype and perforin expression may constitute helpful tools.

Mycosis fungoides (MF), the most common primitive cutaneous T-cell lymphoma, can undergo transformation in about 10% of cases. Transformed mycosis fungoides (T-MF) is often associated with the appearance of a CD20 component. The aim of this study was to analyze whether such cells are reactive or lymphomatous and to evaluate their prognostic impact. Among 311 T-MFs from the French Cutaneous Lymphoma Study Group registry, we studied 148 cases. CD20 was expressed in 88 cases (59%). The proportion of CD20 cells among T-MF lesions was <10% for 54 cases (38%), 10% to 49% for 71 cases (81%), and >50% for 17 cases (19%). We focused the study on 23 cases that contained >50% CD20 cells. To evaluate the nature of the CD20 component, we used immunohistochemistry (2 anti-CD20 antibodies, L26 and 7D1 clones, and 2 other anti-B-cell antigen antibodies, CD22 and PAX5) and a double-stain immunofluorescence technique (anti-CD20 and anti-CD3 antibodies). The clonality of B cells was studied by polymerase chain reaction. Three profiles were observed. In 15 of the 23 cases, the CD20 cells were reactive. In 6 cases, CD20 protein was aberrantly expressed in T-MF lesions. Lastly, there were 2 composite lymphomas (T-MF infiltrate with a B-cell follicular lymphoma). In view of this series, we propose a simple algorithm to help pathologists evaluate the nature of the CD20 component associated with T-MF. Although statistically not significant, there was a trend toward a worse prognosis in the presence of >50% CD20 cells and of a nodular perifollicular pattern of this component.

ObjectiveCongenital haemangiomas (CHs) are rare, benign vascular tumours that are fully developed at birth. Three subtypes of CHs have been described based on clinical behaviour: rapidly involuting CHs (RICHs), non-involuting CHs (NICHs) and partially involuting CHs (PICHs). We explore in our study clinical, evolutionary and paraclinical characteristics of the three CH subtypes.DesignChildren with CH attending our department of paediatric dermatology at Bordeaux University Hospital over a 13-year period were retrospectively included. Epidemiological, clinical and evolutionary data, photographs and imaging results were reviewed. All available tissue samples were histologically examined.ResultsWe included 57 patients: 22 with RICH, 22 with NICH and 13 with PICH. Males predominated (ratio 1.7); the most common CH location was on the limbs. RICH, NICH and PICH exhibited overlapping characteristics; all were single telangiectatic lesions with pale peripheral halos. At birth, NICHs were flat but RICHs and PICHs bulky. The median age at complete RICH involution was 12 months. One-third of CHs that appeared RICH-like at birth underwent incomplete involution to become PICHs. Heart failure and thrombocytopenia were rare complications. PICHs were frequently ulcerated. Pain was common for NICH and PICH. The imaging and histological data of the three CH subtypes were rather similar.ConclusionsWe describe the characteristics and evolution of the three CH subtypes using a case series. Certain overlapping features were apparent, reinforcing the hypothesis that RICH, NICH and PICH lie on the same pathological spectrum.