Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Clinically, LyP is characterized by a variable number of self-healing ...papulo-nodular lesions, with the typical waxing and waning course. Histologically, 4 types (A, B, C, and D) have been delineated. Angioinvasive growth and large ulcers are rare findings in LyP and simulate aggressive lymphoma. We retrospectively analyzed the clinicopathologic and molecular features of angioinvasive LyP in a series of 16 patients. This new form of LyP is characterized by oligolesional papules that rapidly ulcerate and evolve into large necrotic eschar-like lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small-sized to medium-sized atypical lymphocytes expressing CD30 and frequently CD8. As in other forms of LyP, the lesions underwent spontaneous regression after a few weeks. Recurrences were common, but the prognosis was excellent with no extracutaneous spread or disease-related deaths. Complete remission occurred in 9 of 16 patients (56%). This LyP variant should be distinguished from aggressive forms of angiocentric and angiodestructive and cytotoxic T-cell lymphomas. We propose the term LyP type E for this clinically and histologically unusual variant.
Summary
Background
Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently ...recurs after resection. So far, the underlying pathogenesis is largely elusive.
Objectives
To identify genetic alterations by next‐generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH.
Methods
DNA and RNA from an EH lesion of an index patient were subjected to whole‐genome and RNA sequencing. Multiplex PCR‐based panel sequencing of genomic DNA isolated from archival formalin‐fixed paraffin‐embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations.
Results
We identified somatic mutations in genes of the mitogen‐activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low‐frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells.
Conclusions
Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.
What is already known about this topic?
Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour of unknown aetiology.
Cutaneous EH often shows a marked inflammatory infiltrate indicating a reactive origin.
What does this study add?
Half of the samples from cutaneous EH in this study showed activating mutations in the mitogen‐activated protein kinase pathway (MAP2K1 and KRAS).
Mutations were mutually exclusive.
What is the translational message?
Somatic mutations seem to contribute to the formation of a significant proportion of cutaneous EH.
The molecular alterations found might be sensitive for targeted therapies.
Linked Comment: W. Tan and J.S. Nelson. Br J Dermatol 2022; 186:393–394.
Pityriasis lichenoides comprises a clinicopathologic spectrum of cutaneous inflammatory disorders, with the 2 most common variants being pityriasis lichenoides et varioliformis acuta (PLEVA) and ...pityriasis lichenoides chronica. The aim of the study was to describe 13 cases of a unique PLEVA variant characterized in the conspicuous CD30 component and thus mimicking lymphomatoid papulosis (LyP), a condition currently classified in the spectrum of CD30 lymphoproliferative disorders. The cohort included 10 female and 3 male patients whose ages at diagnosis ranged from 7 to 89 years (mean 41 y; median 39 y). The clinical manifestation was that of PLEVA, with small erythematous macules quickly evolving into necrotic papules. No waxing and waning was seen on follow-up in any of the cases. Histopathologically, typical features of PLEVA were present, but an unusual finding was occurrence of a considerable number of CD30 small lymphocytes as detected immunohistochemically. Over half of the cases also displayed a large number of CD8 cells and showed coexpression of CD8 and CD30 in the intraepidermal and dermal component of the infiltrate. Of the 11 cases of PLEVA studied for T-cell receptor gene rearrangement, 6 evidenced a monoclonal T-cell population, and 5 were polyclonal. Parvovirus B19 (PVB19) DNA was identified in 4 of 10 cases investigated, and positive serology was observed for PVB19 in 2 patients, altogether suggesting that PVB19 is pathogenetically linked to PLEVA at least in a subset of cases. The presence of CD30 lymphocytes and CD8 lymphocytes would be consistent with an inflammatory antiviral response, as CD30, even atypically appearing lymphoid cells have been identified in some viral skin diseases. The main significance of the PLEVA variant is, however, its potential confusion with LyP or some cytotoxic lymphomas. Admittedly, the CD30 PLEVA variant described herein and LyP show considerable overlap if one takes into account all known variations of the 2 conditions recognized in recent years, thus suggesting that LyP and PLEVA may be much more biologically closely related entities than currently thought or can even occur on a clinicopathologic spectrum.
Wild-type lectins have distinct types of modular design. As a step to explain the physiological importance of their special status, hypothesis-driven protein engineering is used to generate variants. ...Concerning adhesion/growth-regulatory galectins, non-covalently associated homodimers are commonly encountered in vertebrates. The homodimeric galectin-7 (Gal-7) is a multifunctional context-dependent modulator. Since the possibility of conversion from the homodimer to hybrids with other galectin domains, i.e. from Gal-1 and Gal-3, has recently been discovered, we designed Gal-7-based constructs, i.e. stable (covalently linked) homo- and heterodimers. They were produced and purified by affinity chromatography, and the sugar-binding activity of each lectin unit proven by calorimetry. Inspection of profiles of binding of labeled galectins to an array-like platform with various cell types, i.e. sections of murine epididymis and jejunum, and impact on neuroblastoma cell proliferation revealed no major difference between natural and artificial (stable) homodimers. When analyzing heterodimers, acquisition of altered properties was seen. Remarkably, binding properties and activity as effector can depend on the order of arrangement of lectin domains (from N- to C-termini) and on the linker length. After dissociation of the homodimer, the Gal-7 domain can build new functionally active hybrids with other partners. This study provides a clear direction for research on defining the full range of Gal-7 functionality and offers the perspective of testing applications for engineered heterodimers.
Background
The proportion of Merkel cell carcinomas (MCCs) in solid‐organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes.
...Objective
To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV‐status and identify factors associated with tumour outcomes.
Methods
Retrospective, international, cohort‐study. MCPyV‐status was investigated by immunohistochemistry and polymerase chain reaction.
Results
A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty‐three percent of SOTR MCCs were MCPyV‐positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid‐organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 1.57–7.14, P = 0.002), MCC‐specific mortality (SHR: 2.55 1.07–6.06, P = 0.034) and overall mortality (HR: 3.26 1.54–6.9, P = 0.002). MCPyV‐positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 1.5–13, P = 0.008 and SHR: 3.6 1.1–12, P = 0.032 respectively) in SOTR.
Limitations
Retrospective design and heterogeneity of SOTR cohort.
Conclusions
MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.
This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a ...minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
Cuticular poroma is a rare variant of poroma composed of exclusively or predominantly cuticular cells, namely of large cells with ample eosinophilic cytoplasm. We report 7 cases of this rare tumor ...identified among 426 neoplasms diagnosed as poroma or porocarcinoma. The patients were 4 males and 3 females, ranging in age from 18 to 88 years. All presented with a solitary asymptomatic nodule. The location included knee (2 cases), shoulder, thigh, shin, lower arm, and neck (each 1). All lesions were surgically removed. No evidence of disease was observed in 5 patients with available follow-up (range 12-124 months).Microscopically, all neoplasms were composed of variably sized, focally closed packed, or interconnecting nodules constituted mostly of cuticular cells. Small poroid cells were a focal feature in 5 tumors, whereas in the remaining 2 cases, poroid cells with conspicuous but still in minority. Five neoplasms were somewhat asymmetric, with irregular outlines. Ductal differentiation and intracytoplasmic vacuoles were seen in 6 tumors. Other features variably encountered were conspicuous intranuclear pseudoinclusions, cystic change, occasional multinucleated cells, increased mitoses, and stromal desmoplasia. Four of the 5 tumors analyzed with next-generation sequencing yielded YAP1::NUTM1 fusions. In addition, various mutations, mostly of unknown significance were identified in one neoplasm.
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