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.

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.

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.

[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.

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.

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.

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.

Foreign body reaction to Radiesse: 2 cases.

We report 2 cases of a foreign body reaction to Radiesse, a semipermanent soft-tissue filler consisting of 30% calcium hydroxylapatite microspheres and 70% carboxymethyl cellulose gel carrier. In one case, injection of this filler provoked a nodule on the columella, which was discovered during rhinoplasty. In the second case, the reaction was revealed during histopathologic examination of the deep section of a surgically removed basal-cell carcinoma. Histopathology showed a foreign body reaction with numerous giant cells and histiocytes, some plasma cells, and lymphocytes. Within this inflammatory reaction, a nonpolarizing exogenous material was identified consisting of numerous, round, uniformly sized, yellowish, extracellular deposits with a crackled appearance. Although many authors claim that Radiesse does not induce any foreign body reactions, we found a number of similar histopathologic pictures in studies describing animal or human auricular area test sites or even in reports of lip nodules, which are a well-known adverse effect after injection of this filler into this site. The histopathologic appearance of Radiesse is particularly distinctive and easily recognizable by dermatologists and dermatopathologists.

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.

Miliarial-type perifollicular B-cell pseudolymphoma (lymphocytoma cutis): a misleading eruption in two women.

Disseminated miliarial-type lymphocytoma cutis is a rare clinicopathologic subtype of lymphocytoma, characterized by numerous translucent micropapules and located on the head and neck. We describe here the clinical, histological and immunological features of miliarial-type perifollicular B-cell pseudolymphoma in two women aged 32 and 49 years presenting with numerous 1-2 mm translucent papules on the head and neck. Microscopic examination revealed features typical of a miniature lymphocytoma cutis with a superficial nodular infiltrate housing small well-circumscribed germinal centers containing tingible body macrophages and surrounded by a distinct mantle zone. The immunohistological profile was also typical of lymphocytoma cutis, and polymerase chain reaction analysis of the IgH gene rearrangement did not show any clonal B-cell population. The lesions resolved spontaneously in one case and improved after treatment with hydroxychloroquine in the second patient. The presentation of this subtype of lymphocytoma is a formidable clinical diagnostic challenge. Rosacea, sarcoidosis, democidiosis, lupus miliaris disseminatus faciei and steroid acne are easy to exclude on the basis of histological profile. However, the miliarial form of primary cutaneous center lymphoma is difficult to rule out. Dermatologists and dermatopathologists should be aware of this unusual form of lymphocytoma cutis, which can be misleading during clinical diagnosis.

Eruptive tumors of the follicular infundibulum presenting as hypopigmented macules on the buttocks of two Black African males.

We report two cases of eruptive tumors of the follicular infundibulum (TFI) with an unusual clinical presentation which has not been described previously in literature. In both cases, the appearance was strikingly similar, consisting of multiple asymptomatic hypopigmented macules on the buttocks of two Black African males, aged 38 and 55 years old. In both cases, the eruption had evolved over several months. The individual lesions were of similar size, approximately 1 cm, with irregular and ill-defined borders. Histopathological examination revealed a superficial and horizontal plate-like proliferation of keratinocytes emanating from the epidermis with multiple slender attachments. Pale keratinocytes were present within the epithelial plates. A Fontana stain showed a loss of melanin pigment from the epithelial plates. Orcein (elastic) stain highlighted an increase of the number of the elastic fibers surrounding the tumor. On the basis of these findings, a diagnosis of eruptive TFI was established for both cases. Among the various presentations of TFI, only the eruptive variant appears to be clinically distinctive, with asymptomatic hypopigmented macules usually located on the face, neck and upper trunk. Eruptive TFI should also be added to the clinical differential diagnosis of multiple hypopigmented macules on the buttocks of Black patients.

Tibial lymphoplasmacytic plaque: a new, illustrative case of a recently and poorly recognized benign lesion in children.

Tibial lymphoplasmacytic plaque (TLP) is a recently recognized clinicopathological entity affecting children and is characterized by a linear, reddish brown plaque on the leg with a dense dermal lymphoplasmacytic infiltrate. No effective treatments are available for this lesion of unknown etiology and its course is chronic. We report a new case in which, for the first time, a causative factor (insect bite) is strongly suspected. The clinical and pathological features of TLP may be misleading for the uninformed dermatologist or pathologist. Therefore, we would like to draw attention to this very distinctive clinicopathological presentation in order to help them recognize it easily and prevent it from being misdiagnosed as an infectious disease or, above all, a cutaneous lymphoma. We will discuss the relationship between TLP and linear acral pseudolymphomatous angiokeratoma of children, a variant of pseudolymphoma localized on acral sites in children which may share some of TLP's histopathological features.