Search

Aims: Onychomatricoma (OM), an uncommon benign fibroepithelial neoplasm of the nail unit, is sometimes diagnostically challenging for clinicians and pathologists. OM consistently expresses CD34, but no specific immunohistohemical markers or recurrent genetic alterations have been identified to date. Recent studies have suggested that Wnt signalling is a key molecular characteristic of OM. Methods and results: Ten cases were analysed: four classical OM including two with pleomorphic cells; two superficial acral fibromyxoma‐like variants of OM; three micropapilliferum variants of OM including one with pleomorphic cells; and one proliferating variant of OM. Immunohistochemically, the spindle cells were positive with CD34 (n = 10) and CD99 (n = 1), with focal reactivity for CD10 (n = 5). The epithelial component of the tumours expressed immunopositivity for LEF‐1. Using array comparative genomic hybridization (aCGH), we demonstrated that all OM, including its variants that were tested (n = 8), harboured a few copy number alterations with losses of whole or part of chromosome 13 including the RB1 gene (n = 8) and chromosome 16 (n = 6). Conclusion: We report a recurrent loss of RB1 (13q) as a possible driver molecular event in OM indicating a relationship between OM and other lesions of the spectrum of the so‐called '13q/RB1' family of tumours. We did not identify a role for the Wnt/beta‐catenin signalling pathway, as has been proposed in a recent study. LEF‐1 could be a potential sensitive and specific marker of OM and should be used in the differential diagnosis between OM, superficial acral fibromyxoma, and the CD34‐positive fibrosing family of tumours. [ABSTRACT FROM AUTHOR]

Background: CIC‐rearranged sarcomas (CIC‐RS) represent the most frequent subset of "Ewing‐like" undifferentiated small round cell sarcomas. These tumors tend to be more aggressive than Ewing sarcomas. Moreover, treatment strategy can differ according to teams. The primary aim of this retrospective study was to describe the characteristics, treatments, and outcome for patients with CIC‐RS included in the French NETSARC+ database. Methods: Pediatric and adult patients from 13 French centers with a diagnosis of CIC‐RS were registered from October 2008 to March 2021. Patients and tumors characteristics were collected from the national network NETSARC+ database (http://netsarc.sarcomabcb.org). CIC‐RS diagnosis was pathologically and molecularly confirmed with a central review by expert pathologists. Two groups of patients were studied: those treated as classical Ewing sarcomas (cohort EwS) and those treated as high‐grade soft tissue sarcomas (cohort STS) according to ESMO and/or EpSSG guidelines. Survival was calculated using the Kaplan–Meier method and the log‐rank test was used to compare survival. Results: Among 79 patients, the male/female sex ratio was 0.7 and the median age at diagnosis was 27 years (range 2–87). With a median follow‐up of 37 months, 39 patients died of the disease. Median overall survival from diagnosis was 18 months, with no significant difference between both cohorts (p = 0.9). Nevertheless, when focusing on patients with metastatic disease at diagnosis (N = 21), all patients from cohort STS died of disease while some patients from cohort EwS were still alive and in complete remission. Conclusion: FSG experience confirms the aggressive clinical course of CDS patients regardless of chemotherapy regimen. [ABSTRACT FROM AUTHOR]

The article titled "Onychomatricoma is not a subtype of superficial acral fibromyxoma: Can immunohistochemistry help in the differential diagnosis?" discusses the debate surrounding the classification of onychomatricoma (OM) and superficial acral fibromyxoma (SAFM) as distinct tumors. The authors argue that OM should be recognized as a fibrous neoplasm rather than a fibroepithelial neoplasm, based on their shared immunohistochemical profile and loss of RB1. However, the overall consensus is that OM and SAFM have clinical and histopathologic features that allow for easy differentiation. The article provides distinguishing features between the two tumors and acknowledges that the diagnosis of OM can be challenging in the absence of clinical information or when the nail plate is not submitted for examination. [Extracted from the article]

The article challenges the concept of onychodermis, which is described as an area beneath the nail matrix and nail bed. The authors argue that the concept is confusing and lacks microanatomical basis. They question the claim made by Dr. Lee and colleagues that onychomatricoma is a tumor of onychofibroblasts within the onychodermis. The authors suggest that onychomatricoma is actually a CD34-positive matrix tumor and not an onychofibroblastic tumor. They also discuss their own study on onychomatricoma, which found a link to RB1 loss and suggests the potential diagnostic value of Lef-1. [Extracted from the article]

Background and objective: Average volume‐assured pressure support—automated expiratory positive airway pressure (AVAPS‐AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2‐month AVAPS‐AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health‐related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV. Methods: This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime PaCO2 > 6 kPa, BMI ≥ 30 kg/m2, clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months. Results: Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow‐up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS‐AE group. At baseline, PaCO2 was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS‐AE group (P = 0.032). No significant between‐group difference was observed for objective sleep quality indices. Improvement in PaCO2 was similar between groups with a mean reduction of −0.87 kPa (95% CI: −1.12 to −0.46) in the ST group versus −0.87 kPa (95% CI: −1.14 to −0.50) in the AVAPS‐AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS‐AE group (P = 0.012). Conclusion: AVAPS‐AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange. [ABSTRACT FROM AUTHOR]

In the OS2006 study, patients younger than 18 years were treated with a methotrexate‐based regimen (MTX), patients older than 25 years with a doxorubicin–cisplatin–ifosfamide‐based regimen (API–AI), whereas patients aged 18–25 years received either API–AI or MTX. We herein report the prespecified subgroup analysis of the outcome of 106 patients treated with API–AI. Preoperative chemotherapy combined three doxorubicin–ifosfamide–cisplatin (API) and two doxorubicin–ifosfamide (AI) courses. Postoperative chemotherapy was assigned by risk group: localised patients with a good histological response (<10% viable cells) received two AI and two cisplatin–ifosfamide (PI) courses; patients with synchronous metastases, poor histological response or unresectable primary received five cycles of etoposide–ifosfamide (EI). Of the 106 patients, 61 were randomised to receive or not zoledronate. Median age was 30 years (range 18–67), 66 (62%) patients were >25 years. The primary tumours were axial in 28 patients (26%), and 28 (26%) presented with metastases. Ninety‐six patients (91%) had surgery, conservative in 82 (85%); 36 patients (38%, 95% CI 28–48%) were good responders. Toxicity was manageable, with no significant difference in severe acute toxicity between patients aged >25 years and those younger. With a median follow‐up of 4.8 years, the 5‐year event‐free survival and overall survival rates were 46% (95% CI 36–56) and 57% (95% CI 47–67), respectively. The primary tumour size and initial metastases correlated with a higher risk of event. In these 106 osteosarcoma adult patients, API–AI proved feasible with no excess of toxicity, and favourable activity despite poor‐prognosis factors. What's new? Osteosarcoma paediatric patients are commonly treated with high‐dose methotrexate combined to other active agents. Methotrexate pharmacokinetics varies considerably with age, however, with few prospective studies dedicated to adult patients and currently no consensus concerning the optimal chemotherapy regimen in these patients. This paper describes the population of 106 adult osteosarcoma patients enrolled in the OS 2006 phase III study, their treatment and their outcomes using a chemotherapy backbone without methotrexate that combines doxorubicin, cisplatin, and ifosfamide. This study confirms prior findings that the API‐AI regimen has acceptable toxicity and yields favourable activity in adult osteosarcoma patients with poor prognosis factors. [ABSTRACT FROM AUTHOR]

See related editorial [ABSTRACT FROM AUTHOR]

Aims The nail mesenchyme, as ligamentous connective tissue, is classically described as a single compartment. Some authors have even suggested the concept of the nail as a musculoskeletal appendage. Recent studies conducted on supernumerary digits surgically removed for polydactyly or on the developing nail organ have introduced into the literature a new concept: the onychodermis and its onychofibroblasts that are CD10-positive/ CD34-negative. The aim of this study was to explore the nail mesenchyme more comprehensively. Methods and results A series of 10 normal adult nail units were examined with a combination of morphological and immunohistochemical analysis. This study demonstrates that the nail mesenchyme has two distinct compartments, with a complex microanatomy of matrical dermis and its hypoderm. The matrical dermis is a relatively independent substructure, and comprises two parts: a thin papillary dermis, and a relatively thick reticular dermis. The matrical hypoderm corresponds to a cushion-like layer of adipose tissue, which distally intermingles with an area of loose connective tissue. The nail bed dermis comprises a single, relatively homogeneous compartment. Conclusion The matrical nail mesenchyme is a modified dermis. The concept of onychodermis is not applicable in the normal adult nail. Underrecognized non-pathological structures may pose diagnostic problems. The chameleon matrical hypoderm is one such structure. [ABSTRACT FROM AUTHOR]

BACKGROUND: A significant improvement in overall survival (OS) was demonstrated in patients with advanced hepatocellular carcinoma (HCC) who received sorafenib (Sor) in the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, in contrast to a response rate (RR) of 2% assessed according to Response Evaluation Criteria in Solid Tumors (RECIST). Modified RECIST (mRECIST) were developed to assess the response in patients with HCC, based on measurement of viable tumor with arterial enhancement on a computed tomography (CT) scan. In the current study, mRECIST were evaluated and were compared with RECIST in patients who received Sor for advanced HCC. METHODS: The authors retrospectively analyzed 53 patients who received Sor for advanced HCC. Patients must to have undergone a 4-phase CT scan before treatment and repeatedly thereafter. CT scans were analyzed using RECIST 1.1 and mRECIST. RESULTS: The rates of objective response (OR), stable disease (SD), and progressive disease (PD) were 2%, 79%, and 19%, respectively, according to RECIST and 23%, 57%, and 21%, respectively, according to mRECIST ( P < .001). Patients who achieved an OR according to mRECIST had a longer OS than nonresponding patients with SD or PD (median OS, 18 months and 8 months, respectively; P = .013). In the 42 patients who achieved SD according to RECIST, OS differed depending on tumor response according to mRECIST, with a median OS of 17 months, 10 months, and 4 months for patients who achieved an OR (n = 11), SD (n = 29), and PD (n = 2), respectively ( P = .016). CONCLUSIONS: The current series validated mRECIST in patients who received Sor for advanced HCC. The majority of patients who had SD according to RECIST had a different prognosis according to mRECIST. The results indicated that, for patients with HCC, mRECIST should be used for the standard assessment of treatment efficacy, particularly in patients who are receiving antiangiogenic drugs. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

This article describes two cases of junctional epidermolysis bullosa in nonrelated kittens. Both cats exhibited pinnal erosions, oral ulcerations and severe onychomadesis. Histopathology, electron microscopy and/or indirect immunoperoxidase revealed subepidermal clefting, with the lamina densa remaining attached to the floor of the vesicles. Indirect immunofluorescence revealed reduced staining for laminin-5γ2 subunit in case 1 andβ3 subunit in case 2. [ABSTRACT FROM AUTHOR]

In order to describe the characteristic signs and course of a possibly new clinical entity, we undertook a clinical study of a series consisting of four families (5 children and 10 relatives) with a distinctive eruption of the tongue. The disease always started in a child, usually an Infant (mean age 152 months), and then spread to one or several other members of the family. It had an abrupt onset and was characterized by difficulties in feeding, Increased salivation, and irritability Inflamed, hypertrophic fungifom paplllae were seen on the tip and the dorsolateral part of the tongue, sons having a pseudopustular appearance. There were no vesicles, erosions, signs of geographic tongue, or oral thrush; the central part of the tongue, the lips, gingivae, palate, and throat were normal. The acute phase lasted 6 to 7 days and was self-limited A few days later, one or several relatives experienced an intense burning sensation on the tongue, with an Increase and exacerbation caused by food intake, with the identical features of inflamed paplllae. The duration of the stomatits he was usually 1 week for the infants, but longer for some adults. The similarity of these cases suggests the existence of a new clinical entity possibly of viral origin. We propose naming this eruption `eruptive familial lingual papiIlitis. [ABSTRACT FROM AUTHOR]

Erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies. We studied the plasma from 272 patients with hormone‐receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) MBC to detect 17 ERBB2 mutations using a screening assay. The assay was developed on the three‐color Crystal dPCR™ naica® platform with a two‐step strategy for precise mutation identification. We found that nine patients (3.3%) harbored at least one ERBB2 mutation. The mutation rate was higher in patients with lobular histology (5.9%) compared to invasive breast carcinoma of no special type (2.6%). A total of 12 mutations were found with the following frequencies: L755S (25.00%), V777L (25.00%), S310Y (16.67%), L869R (16.67%), S310F (8.33%), and D769H (8.33%). Matched tumor samples from six patients identified the same mutations with an 83% concordance rate. In summary, our highly sensitive multiplex digital PCR assays are well suited for plasma‐based monitoring of ERBB2 mutational status in patients with MBC. [ABSTRACT FROM AUTHOR]