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.

Adenomatoid tumor of the skin: Differential diagnosis of an umbilical erythematous plaque.

Adenomatoid tumors are benign tumors of mesothelial origin that are usually encountered in the genital tract. Although they have been observed in other organs, the skin appears to be a very rare location, with only one case reported in the literature to our knowledge. We report a second case of an adenomatoid tumor, arising in the umbilicus of a 44-year-old woman. The patient presented with an 8-month-old erythematous and firm plaque under the umbilicus. A skin biopsy showed numerous microcystic spaces dissecting a fibrous stroma and lined by flattened to cuboidal cells with focal intraluminal papillary formation. This little-known diagnosis constitutes a diagnostic pitfall for dermatopathologists and dermatologists, and could be misdiagnosed as other benign or malignant entities. Through this case report, a practical approach and diagnostic keys have been devised to avoid misdiagnosis and overtreatment.

Direct examination, histopathology and fungal culture for the diagnosis of onychomycosis: A retrospective, comparative study on 2245 specimens.

BACKGROUND: Onychomycosis affects 5.5% of the general population and represents up to 50% of all nail diseases. Diagnosis and pathogen identification are essential in order to plan an adequate treatment. Many diagnostic techniques are available, and however, no solid data regarding comparison between different techniques over a large number of specimens are available to date. OBJECTIVES: To compare sensitivity and specificity of direct examination, histopathology and fungal culture in our referral mycology laboratory. METHODS: Nail specimens received at the cutaneous pathology and mycology laboratory of the University Hospital Saint-Pierre (Brussels, Belgium) between 1 January and 15 May 2018 were retrospectively analysed. All specimens were submitted to direct examination and culture. In cases of adequate specimen size, histopathology was performed. Fungal culture was considered the gold standard for diagnosis. RESULTS: A total of 2245 nail samples were included in the study. Onychomycosis was diagnosed in 1266 specimens. Sensitivity and positive predictive value were found to be higher for direct examination compared to histopathology, while sensitivity of direct examination was found to be lower. Combined approach with all the three techniques showed the highest rate of positivity, followed by the association of direct examination and histopathology. CONCLUSIONS: To our knowledge, this study included the largest number of nail specimens to date, allowing a comparison between direct examination, culture and histopathology. Direct examination showed to be the most performing technique in routine practice. Histopathology represents the most effective option in cases where both specimen size and laboratory resources are adequate. Our paper adds to the literature the 'real-life' experience of the mycology laboratory of a referral centre for nail diseases.

Chilblains.

Idiopathic chilblain is a relatively common yet poorly recognized acrosyndrome. This literature review aims to better understand and draw attention to this disorder. Chilblain is a localized inflammation of the skin that occurs on exposure to cold but non-freezing wet weather. It usually resolves spontaneously. The etiology is uncertain, but vasospasm seems to play a role in this abnormal reaction to cold. Diagnosis is most often based on clinical presentation, but a skin biopsy can be useful in dubious cases. In histology, dermal edema and an inflammatory infiltrate are usually present. A distribution of the infiltrate particularly around the eccrine gland is typical. Systemic symptoms and underlying autoimmune disease should be screened. Avoiding cold and keeping extremities warm is the first recommendation for management, as well as smoking cessation. Calcium channel blockers (in particular nifedipine) seems to be the treatment that has been most evaluated in chilblains. However, their effectiveness is not confirmed by all studies. Topical betamethasone is often used but its effect has not been confirmed by randomized clinical trials. Other treatments, such as pentoxifylline, hydrochloroquine and topical nitroglycerin have shown positive effects only in a reduced number of patients. Acupuncture seems to bring a benefit.

Immunohistochemical characterization of benign activation of junctional melanocytes and melanoma in situ of the nail unit.

BACKGROUND: Immunohistochemical (IHC) stains that distinguish benign, pigmented nail lesions from malignancy are needed. Candidate markers of malignant transformation include p16, HMB45, and Ki-67, with p16 being of particular interest. There is limited knowledge about the spectrum of p16 expression in pigmented lesions, especially junctional melanocytic proliferations of the nail. The objective of this study was to determine if any of these markers demonstrate diagnostic utility in distinguishing between benign activation of junctional melanocytes (BAM) and melanoma in situ (MIS) of the nail unit. METHODS: In this retrospective study, ten cases of BAM and eight cases of MIS were identified. Archival slides available for review included H&E (hematoxylin and eosin), Fontana-Masson, and MelanA (Mart1) IHC slides. IHC studies for p16, HMB45, and dual-color Ki-67/MelanA (Mart1) were then performed. RESULTS: None of the tested IHC stains distinguished BAM from MIS. p16 IHC expression was uniformly negative with the exception of two cases of MIS. HMB45 was positive in all BAM and MIS cases. Ki-67/MelanA showed positive Ki-67 staining of MelanA-positive melanocytes in two cases of MIS, and all other cases of MIS and BAM were negative for Ki-67. The two positive p16 and two positive Ki-67/MelanA cases were non-overlapping. CONCLUSION: p16, HMB45, and Ki-67/MelanA IHC studies show no apparent utility in distinguishing BAM from MIS in the nail unit.

Treatment of Ingrowing Toenails With Phenol 88% or Trichloroacetic Acid 100%: A Comparative, Prospective, Randomized, Double-Blind Study.

BACKGROUND: Phenol is the gold standard for chemical matricectomy in ingrowing toenail. Recently, trichloroacetic acid (TCA) was used as cauterant. Both agents have high success rates but a postoperative healing time claimed to be faster for TCA rather than phenol. OBJECTIVE: Comparing the efficacy, the postoperative oozing time, the inflammatory reaction, and the postoperative pain. MATERIALS AND METHODS: Comparative, prospective, randomized, double-blind study. Eighty-four patients with 96 ingrowing toenails were randomized in 2 groups. Forty-six ingrowing toenails were treated with phenol 88% and 50 with TCA 100% within a 4-month period. Patients were observed 4 times for the presence of oozing and for the degree of inflammation. Patients assessed also oozing and pain on a scale basis during 34 days. RESULTS: Oozing was observed to be less with phenol treatment, as from the second week. Inflammation was also significantly inferior in the phenol group at Week 4. Patients evaluated the incidence of pain below 2/10 for both cauterants, while oozing was higher with TCA during 34 days. The overall success rates of both groups were similar with 100%. CONCLUSION: Phenol and TCA are both effective but TCA does not offer any advantage in terms of postoperative morbidity compared with phenol.

An international survey about nail histology processing techniques.

BACKGROUND: There are limited data on nail histopathology techniques. The objective of this study was to examine nail histopathology techniques currently in use internationally. METHODS: An online survey was sent to the European Nail Society and Council for Nail Disorders during 2015-2016. RESULTS: There were 57 respondents, from twenty countries comprising dermatologists, podiatrists and pathologists. Specimens were unmarked or marked using ink or a suture and fixed in 10% formalin, from 6 to 48 hours before embedding in paraffin wax (90% [17/19]), liquid nitrogen (frozen section, 1/19) and 2-hydroxyethylmethacrylate (plastic, 1/19). Nail softening was undertaken by 71% (17/24) of respondents for 6 to 48 hours using Mollifex Gurr (12.5%, 3/24), 10% potassium hydroxide solution (12.5%, 3/24) or 10% potassium thioglycolate cream (12.5%, 3/24). Section thickness was 4 to 9 µm (62.5%), using a steel microtome (92%,12/13) on glass slides (91.6%, 11/12). Hematoxylin and eosin (H&E) was routine for all biopsies and Periodic acid Schiff (PAS) for fungus. The favored stain for differentiating melanin and hemoglobin was Fontana-Masson (60%, 6/10). For pigmented lesions, Melan-A was always employed by all respondents (9/9). CONCLUSION: Nail histopathology processing has some small variations from normal skin processing.

Pseudoangiomatous xanthelasmoid mastocytosis: two case reports showing the hypervascularity of this rare variant of cutaneous mastocytosis.

Xanthelasmoid mastocytosis or xanthelasmoidea is a rare clinical variant of cutaneous mastocytosis characterized by a yellow hue of the clinical lesions, which are often misdiagnosed as juvenile xanthogranuloma. We present two pediatric cases of xanthelasmoid mastocytosis presenting as isolated mastocytomas, which are notable histopathologically for their hypervascularity. This pseudoangiomatous variant of cutaneous mastocytosis is important for pathologists to have knowledge of, so that a diagnosis of a vascular tumor is not rendered accidentally. The yellow hue has previously been explained by the usual deep and solid dermal mast cell infiltrate. In the two presented cases, however, the mast cell infiltrate was sparse, and the yellow color cannot be related to infiltrate density. We believe that the hypervascularity is at least one factor in the production of clinical xanthelasmoid appearance, and we propose the term 'pseudoangiomatous xanthelasmoid mastocytosis' to properly describe this rare variant of cutaneous mastocytosis.

Macular arteritis associated with concurrent HIV and hepatitis B infections: a case report and evidence for a disease spectrum association with cutaneous polyarteritis nodosa.

We report the first case of macular arteritis in a 33-year-old Black, African female with concurrent human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Of particular interest in macular arteritis is the striking discordance between the clinical presentation and the histopathological findings, a fact that both dermatologists and dermatopathologists should be aware. Histopathologically, the case showed typical findings of macular arteritis with a perivascular, predominantly lymphocytic, infiltrate and intraluminal thrombosis. Both HIV and HBV have been reported as viral inducers of cutaneous polyarteritis nodosa (PAN). Their association with macular arteritis in this case supports existing evidence that macular arteritis and cutaneous PAN represent a single-disease spectrum of vasculitides, with macular arteritis representing the chronic, lymphocytic and indolent stage, and cutaneous PAN the neutrophilic, acute stage with a risk for systemic progression. Lymphocytic thrombophilic arteritis (LTA), a third, uncommon disease would be in between macular arteritis and cutaneous PAN on a spectrum. Features of this case and other published cases provide strong evidence that there is a single, mild-to-severe disease spectrum of macular arteritis-LTA-cutaneous PAN.

Nail cosmetology.

Nail cosmetics is enjoying growing success due to recent technological advances. Manicures can be responsible for mechanical, infectious or allergic adverse effects. Nail cosmetics (e.g., nail varnishes, acrylic false nails, light-curing gels, and adhesive false nails) incorporate substances that harden after solvent evaporation or after polymerization. Allergic reactions can occur, remotely with conventional varnishes and locally with polymerizing substances. Artificial nails incur a risk of carrying infectious agents which can cause serious infection, and should not be used by caregivers. Recently, there has been a worrisome increase in the frequency of acrylate allergy, due to the appearance of home kits and lack of information in the general public. The infectious, allergic and toxic risks incurred by consumers and professionals regarding manicure or pedicure treatments and the application of nail cosmetics are the subject of recommendations and monitoring measures.

Tangential excision of pigmented nail matrix lesions responsible for longitudinal melanonychia: evaluation of the technique on a series of 30 patients.

OBJECTIVES: We sought to assess the shave biopsy technique, which is a new surgical procedure for complete removal of longitudinal melanonychia. We evaluated the quality of the specimen submitted for pathological examination, assessed the postoperative outcome, and ascertained its indication between the other types of matrix biopsies. DESIGN: This was a retrospective study performed at the dermatologic departments of the Universities of Liège and Brussels, Belgium, of 30 patients with longitudinal or total melanonychia. RESULTS: Pathological diagnosis was made in all cases; 23 patients were followed up during a period of 6 to 40 months. Seventeen patients had no postoperative nail plate dystrophy (74%) but 16 patients had recurrence of pigmentation (70%). LIMITATIONS: This was a retrospective study. CONCLUSIONS: Shave biopsy is an effective technique for dealing with nail matrix lesions that cause longitudinal melanonychia over 4 mm wide. Recurrence of pigmentation is the main drawback of the procedure.

A retrospective study of squamous cell carcinoma of the nail unit diagnosed in a Belgian general hospital over a 15-year period.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant tumor at the nail unit. It mainly affects middle-aged men, with a peak incidence between 50 and 69 years of age. Diagnosis is often delayed because of the slow evolution of the lesion and multiple clinical features. OBJECTIVE: We sought to characterize the different clinical and histopathological patterns of SCC of the nail unit and evaluate their therapeutic outcome. METHODS: Records for 58 patients were retrieved from our department's dermatopathology database over a period of 15 years (1995-2011) and the patients recontacted. RESULTS: Of the 58 patients, 51 were eligible for follow-up. There was a male predominance (72.5%). The fingers were most commonly affected (98%), the right index and long fingers being most commonly affected (20.8% each). The nail bed was mainly affected. The commonest clinical signs were, in decreasing order, subungual hyperkeratosis, onycholysis, oozing, and nail plate destruction. The majority of SCC of the nail unit was in situ (63%). The recurrence rate of all treatments taken together was 30.6%. LIMITATIONS: Retrospective study design is a limitation. CONCLUSIONS: SCC of the nail unit mostly affects men aged 50 to 69 years. Most cases were the warty type, with oozing being an underrecognized clinical sign. Contrary to prior studies, most lesions were in situ, and bone involvement was uncommon. Conservative surgical resection should be the first-line treatment when the bone is not involved. Recurrence rate is high when a procedure other than Mohs micrographic surgery is performed.

Refractory Trichophyton rubrum infection in lamellar ichthyosis.

A 10-month-old boy with congenital lamellar ichthyosis presented with a chronic Trichophyton rubrum infection. There was no history of atopy or immunosuppression, and examination revealed high total immunoglobulin E (IgE) with a positive specific IgE for T. rubrum. Multiple treatments with fluconazole were necessary to control the infection. T. rubrum is present worldwide and is responsible for the vast majority of chronic dermatophytosis. Lamellar ichthyosis is a risk factor for chronic dermatophytosis because of excessive keratin and the barrier defect. A delayed-type hypersensitivity reaction to T. rubrum is associated with cure, whereas immediate hypersensitivity and IgE are not protective and may lead to chronic infection. Atopy and the Th2 profile therefore seem to be associated with chronic dermatophytosis. The association between ichthyosis and atopy is well documented. T. rubrum also has an interesting ability to evade immunity, which helps explain the chronic infection. Finally, in ichthyosis, it is likely that fluconazole has difficulty penetrating the acanthotic stratum corneum, which explains treatment failure. We report this case to alert clinicians to the possible association between lamellar ichthyosis and chronic dermatophytosis and to report the difficulties of management.

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.

Cryopyrin-associated periodic syndrome: an autoinflammatory disease manifested as neutrophilic urticarial dermatosis with additional perieccrine involvement.

A female newborn presented with a congenital urticarial rash that consisted of fluctuating well-demarcated pink or pale reddish macules or slightly raised papules and plaques. In addition, purulent cerebrospinal fluid was present in the absence of evidence of congenital infection. Skin biopsy revealed a sparse infiltrate throughout the entire dermis, including the eccrine adventitia. The infiltrate was composed mostly of neutrophils, but rarely lymphocytes and eosinophils could also be seen. No vasculitis was present. Because of the presenting attributes, a diagnosis of cryopyrin-associated periodic syndrome (CAPS) was considered and the neonatal-onset multisystem inflammatory disorder (NOMID) that represents the most severe expression of the CAPS clinical spectrum was favored. Diagnosis was confirmed by identification of a mutation in the cold-induced autoinflammatory syndrome-1 gene and by an observed response to treatment with the interleukin-1 receptor antagonist anakinra. Both the clinical and histopathological findings of the presented case may represent a distinct entity within the spectrum of aseptic neutrophilic dermatitis. We refer to this spectrum as neutrophilic urticarial dermatosis (NUD), which may serve as a cutaneous marker of autoinflammation. NUD with perieccrine involvement should prompt consideration of CAPS, especially NOMID, in the context of neonatal multisystem disease.

Immunohistochemical study of 40 cases of longitudinal melanonychia.

The etiology of longitudinal melanonychia (LM) is difficult to establish by clinical and dermoscopic examinations alone. Microscopic examination of the nail matrix remains crucial. Two groups of LM may be identified: melanocytic activation (melanic pigmentation of the matrix epithelium without any increase in the density of melanocytes) and melanocytic proliferation (lentigo, nevus, or melanoma). The histological examination is challenging, and immunohistochemical investigations can be helpful. The objective of this study was to analyze the immunohistochemical findings with routinely used markers in melanocytic tumors-S-100 protein, HMB-45, and Melan-A-in LM. A series of 40 cases were analyzed: 10 activations, 4 lentigines, 7 nevi, 12 in situ melanomas, and 7 invasive melanomas. The sensitivity of S-100 protein is weak in benign and malignant intraepithelial melanocytes of the nail matrix, and if this marker is performed alone, it may be wrongly reassuring. However, the use of S-100 protein is essential to differentiate invasive melanoma, lacking an intraepithelial component, and particularly desmoplastic melanoma, from epithelial and mesenchymal tumors. HMB-45 and Melan-A are more sensitive than S-100 protein for the evaluation of intraepithelial melanocytic proliferation of the nail apparatus, with HMB-45 being the most intense marker. In the dermal component, HMB-45 and Melan-A were less sensitive than S-100 protein. In conclusion, we recommend that the panel of antibodies used for histological evaluation of LM should include HMB-45 and/or Melan-A and S-100 protein only if an invasive melanoma is suspected.