Re-evaluation of the concept of basaloid follicular hamartoma associated with naevoid basal cell carcinoma syndrome: a morphological, immunohistochemical and molecular study.

Naevoid basal cell carcinoma syndrome (NBCCS) is a rare genodermatosis caused by germline mutations in genes of the Sonic Hedgehog (SHH) pathway and is characterised by early onset of multiple basal cell carcinomas (BCCs). Although skin tumours with follicular differentiation, notably basaloid follicular hamartoma (BFH), have been reported in NBCCS, their relations with BCC are poorly defined. In this context, the aim of this study was to clarify morphological, immunohistochemical â€‹and molecular features of BFH arising in a context of NBCCS. A total of 140 skin tumours from NBCCS and 140 control BCC tumours were reviewed, blinded to clinical data and classified as BCC or BFH. The morphological characteristics of these two groups were then compared. Twenty cases were submitted for immunohistochemical and molecular analysis. Thirty-three tumours among the exploratory cohort were classified as BFH and were exclusively detected in NBCCS patients. Histopathological criteria that were significantly different from BCC were as follows: a small size (<1.5 mm), connection to a hair follicle, arborescent organoid architecture, lack of cytological atypia and infundibulocystic differentiation. Immunohistochemical analysis confirmed activation of the SHH pathway in these lesions. Targeted next-generation sequencing suggested that MYCN and GLI2/3 amplifications and TP53 mutations might be involved in progression of these follicular tumours to BCC. Our study confirms the high prevalence of BFH, representing up to 24% of skin tumours in NBCCS and potentially being BCC precursors.

Three atypical/malignant onychopapillomas in a 52-case series with immunohistochemical study.

BACKGROUND: Onychopapilloma (OP) is a benign tumor of the nail. Haneke reported one case of malignant OP in 2021. No systematic immunohistochemistry study has been conducted on OP. The aim of our study was to identify possible malignant OP in our series of OP and to describe the immunohistochemical expression of p16, p53, and Ki67 in typical and atypical/malignant ones. METHODS: Ninety-one cases were available for pathological review. Immunohistochemical analysis could be performed on 52 cases. RESULTS: In 88 of 91 cases, the diagnosis of OP was confirmed. Three atypical/malignant cases were observed. No OP expressed p16. A normal p53 expression was observed in two thirds of the cases, an abnormal increased p53 expression in one third, including the three atypical cases. A normal Ki67 expression was observed in 84% of the cases, an abnormal Ki67 expression with focal heterogeneous expression in the suprabasal layers in 6% and in all suprabasal cell layers in 10%, including the three atypical cases. CONCLUSIONS: The diagnosis of atypical/malignant OP may be underestimated. The expression of Ki67 and p53 in these tumors differs from the expression observed in conventional OP. The absence of p16 expression confirms that human papillomavirus does not play a role in the etiopathogenesis of OP.

Sweat Gland Tumors Arising on Acral Sites: A Molecular Survey.

Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in digital papillary adenocarcinoma (DPA). The main objectives of the present study were (i) to provide an overview of the prevalence of previously identified oncogenic drivers in acral sweat gland tumors and (ii) to genetically characterize tumors in which no recurrent genetic alteration has been identified yet. Cases of acral sweat gland tumors were identified from the database of the French network CARADERM. After histologic review, the presence of previously identified genetic alterations was investigated in the entire cohort (n=79) using a combination of immunohistochemistry and targeted DNA and RNA sequencing. Tumor entities with no recurrent genetic alterations were submitted to whole-transcriptome sequencing. CRTC1::MAML2 fusion was identified in cases of hidradenoma and hidradenocarcinoma (n=9/12 and n=9/12). A p.V600E mutation of BRAF was observed in all cases of tubular adenoma (n=4). YAP1:MAML2 and YAP1::NUTM1 fusions were observed in poroid tumors (n=15/25). ETV6::NTRK3 and TRPS1::PLAG1 fusion transcripts were identified in secretory carcinoma (n=1/1) and cutaneous mixed tumors (n=3/4), respectively. The HPV42 genome was detected in most cases of DPA (n=10/11) and in 1 adnexal adenocarcinoma not otherwise specified. Finally, whole-transcriptome analysis revealed BRD3::NUTM1 or NSD3::NUTM1 fusions in 2 cases of NUT adnexal carcinoma and NCOA4::RET and CCDC6::RET fusion transcripts in 2 cystadenoma/hidrocystoma-like tumors. Our study confirms distinctive cytogenetic abnormalities in a wide number of acral adnexal neoplasms and supports the use of molecular analysis as a valuable aid in the diagnosis of these rare and often difficult to diagnose group of neoplasms.

MRI of squamous cell carcinoma of the nail apparatus: report of 6 cases.

Malignant tumors of the nail apparatus are rare and dominated by squamous cell carcinomas (SCC). Routinely, their pre-therapy imaging is limited to radiography. Our purpose is to determine the MRI characteristics in the locoregional assessment of SCC of the nail apparatus through a series of 6 consecutive cases explored by MRI and operated, carried out over a period of 12 years. IRB approval was obtained. Two in situ and 4 invasive squamous cell carcinomas were found, sex ratio was 0.5, and the age was 55 ± 10 years (mean ± SD). Most tumors showed specific signal behavior different from that of the epidermis and dermis with high signal on T2wi (5/6) and complete or partial enhancement (6/6). The mean thickness was 3.4 mm. The deep margin of the tumor with the dermis was always well defined for Bowen's disease (2/2) and blurred for invasive SCC. Localization involved the nail bed epithelium in all cases. Changes of the nail plate were detectable. Extension to lateral and posterior folds, hyponychium, cul-de-sac matrix, deep dermis, and bone was determined. MRI could be proposed as preoperative imaging of squamous cell carcinoma for locoregional assessment and guide biopsy.

Recurrent FOXK1::GRHL and GPS2::GRHL fusions in trichogerminoma.

We report 21 cases of trichogerminoma harbouring previously undescribed FOXK1::GRHL1/2 or GPS2::GRHL1/2/3 in-frame fusion transcripts. Microscopic examination of a preliminary set of five cases revealed well-delimitated tumours located in the dermis with frequent extension to the subcutaneous tissue. Tumours presented a massive and nodular architecture and consisted of a proliferation of basaloid cells. A biphasic pattern sometime resulting in tumour cell nests ('cell balls') was present. Immunohistochemistry demonstrated the expression of cytokeratins (CKs) 15, 17, and PHLDA1. In addition, numerous CK20-positive Merkel cells were detected. RNA sequencing (RNA-seq) revealed a FOXK1::GRHL1 chimeric transcript in three cases and a FOXK1::GRHL2 fusion in two cases. In a second series for validation (n = 88), FOXK1::GRHL1/2 fusion transcripts were detected by RT-qPCR or FISH in an additional 12 trichogerminomas and not in any other follicular tumour entities or basal cell carcinoma cases (n = 66). Additional RNA-seq analysis in trichogerminoma cases without detected FOXK1::GRHL1/2 rearrangements revealed GPS2::GRHL1 fusion transcripts in two cases, GPS2::GRHL2 in one case, and GPS2::GRHL3 fusion transcript in one case. Therefore, our study strongly suggests that GRHL1/2/3 gene rearrangements might represent the oncogenic driver in trichogerminoma, a subset of follicular tumours characterized by immature features and numerous Merkel cells. © 2022 The Pathological Society of Great Britain and Ireland.

[Extra Mammary Paget disease]. / Maladie de Paget extra-mammaire.

Extramammary Paget's disease is a rare malignancy. The underlying cause of VPD remains not well understood. We provide an overview of the histopathology of vulvar Paget's disease, with or without invasion.

Nail Unit Blue Nevi: A 11-Case Series and Review of the Literature.

BACKGROUND: Blue nevus of the nail apparatus is a rare entity and only isolated cases are reported in the literature. OBJECTIVE: The aim of this study was to better characterize blue nevus at the nail unit. METHODS: Retrospective analysis of all nail unit blue nevi from the Nail Group of the French Society of Dermatology was compared to the literature. RESULTS: Eleven cases were retrieved from 2002 to 2019 with an average age of 45 years. The majority were women (9/11) and acquired (10/11). Hands were more frequently involved (9/11) with a predilection for the thumb and 2 cases were located on the hallux. Nail unit blue nevus mostly presented as a well-delimited blue spot of the lunula (9/11) and histologically was of the common type (10/11). There was no malignancy. CONCLUSION: Nail unit blue nevus is a rare asymptomatic benign entity, mostly acquired on the thumb or the hallux of women. The most frequent presentation is a painless blue spot on the lunula. Congenital blue nevi seem to only affect the paronychium. Main differential diagnosis is melanoma and histopathological examination is mandatory.

Successful Treatment of Generalized Eruptive Keratoacanthoma of Grzybowski with Acitretin.

INTRODUCTION: Keratoacanthomas (KA) are common cutaneous skin tumors originating from the hair follicles. Unlike squamous cell carcinoma, KA can regress spontaneously and have a benign evolution. Solitary KA is the most common form but familial multiple KA (Ferguson-Smith type), genetically predisposed KA (such as in xeroderma pigmentosum, or Muir-Torre syndrome), or sporadic multiple eruptive KA (Grzybowski type) have been described. Generalized eruptive KA of Grzybowski (GEKA) is a rare condition (around 40 reported cases). The pathophysiology is still unclear. Human papillomavirus (HPV) has been detected in sporadic KA but the presence of HPV39 has never been reported, to our knowledge, in GEKA. CASE REPORT: GEKA in an 80-year-old woman was successfully treated with acitretin (0.5 mg/kg/day) combined with surgical removal of the largest lesions. Treatment was well tolerated and led to decreased pruritus and tumor regression within 6 months. The presence of HPV39 was detected in a lesion by polymerase chain reaction and Sanger sequencing. No genetic alteration was found, in particular in the genes usually altered in squamous cell carcinoma (including NOTCH1, NOTCH2, CDKN2A, TP53). CONCLUSION: We report a case of GEKA associated with the presence of HPV39 and the successful use of acitretin combined with surgical removal of the larger lesions.

Plaque-Like Myofibroblastic Tumor: Report of 4 Cases.

Plaque-like myofibroblastic tumor of infancy was first characterized in 2007 by Clarke et al. In the first 2 cases described, large plaque-like tumors presented in the first 3 months of life exhibited microscopic features consistent with dermatofibroma but with immunohistochemical features of myofibroblastic lineage. In 2013, Marqueling et al reported 3 additional cases, 2 of which presented in early childhood, prompting the authors to recommend that the name of this condition be shortened to plaque-like myofibroblastic tumor. We present here 4 additional cases to better characterize clinical and histopathological features of this newly recognized entity. This benign lesion is of myofibroblastic lineage and demonstrates features consistent with multiple clustered dermatofibroma.

Histopathologic and Ultrastructural Features of Gold Thread Implanted in the Skin for Facial Rejuvenation.

The authors report the histopathologic and ultrastructural features of gold threads, which were implanted in the cheek subcutis of a 77-year-old woman 10 years ago. These particles did not give rise to any adverse reactions and were fortuitously discovered by the surgeon during a facelift. Histopathology showed a nonpolarizing exogenous material consisting of black oval structures surrounded by a capsule of fibrosis and by a discrete inflammatory reaction with a few giant cells. In some cases, only a long fibrous tract surrounded by a moderate mononucleate infiltrate was observed. The wires were characterized with scanning electron microscopy, and X-ray microanalysis revealed a specific peak at 2.2 keV representative of gold that was absent in the control skin sample. As this value is specific for gold, it confirms the presence of the metal in the patient's skin. The histopathologic appearance of gold threads is particularly distinctive and easily recognizable by dermatopathologists.

Alginate (novabel): a new class of injectable filler.

A new class of biodegradable, injectable filler made of alginate, Novabel (Merz Aesthetics, Merz Pharma, UK), was launched in the European market in 2010. This product was supposed to be perfect to fill hollow eye rings and practitioners were immediately enthusiastic. Unfortunately, complications occurred as firm inflammatory nodules after a few months. Histological examinations revealed granulomatous reactions around spheroidal deposits. Treatment by triamcinolone injections was effective in some cases. Because of these complications, the company withdrew the alginate Novabel from the market. This is a didactic example of how a well-meant development with an insufficient test phase can turn into its opposite. Health authorities are exhorted to supervise not only drugs, but also injectables and other medical devices before they are launched, and during their application.

Syringotropic mycosis fungoides: clinical and histologic features, response to treatment, and outcome in 19 patients.

BACKGROUND: A rare variant of mycosis fungoides (MF), syringotropic MF (STMF) is characterized by a particular tropism of the lymphocytic infiltrate for the eccrine structures, and included in the follicular subtype of MF in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. OBJECTIVE: We sought to determine the clinicopathologic features and disease course of patients with STMF. METHODS: A retrospective study was conducted to identify patients with STMF from 1998 to 2013. RESULTS: Nineteen patients were included: 15 men and 4 women, mean age 55 years (range, 24-86). Most had multiple lesions (n=16, 84%) with associated alopecia (n=12, 63%) and/or punctuated aspect (n=12, 63%). Palms or soles were involved in 10 cases (53%). Folliculotropism was found in 13 cases (68%). After a median follow-up of 70 months (range, 2-140), 3 patients died, 1 from disease-related death. The 5-year overall and disease-specific survival were 100%. The disease-specific survival was significantly higher than in 54 patients with folliculotropic MF without syringotropism (5-year disease-specific survival, 74%; 95% confidence interval, 58%-94%, P=.02). LIMITATIONS: Retrospective setting is a limitation. CONCLUSIONS: In the spectrum of adnexotropic MF, STMF appears as a distinct entity from follicular MF, with peculiar clinical characteristics and natural history.