Clinical and pathological features of Merkel cell carcinoma: A 4-year follow-up observational retrospective study in Spain.

BACKGROUND: Merkel cell carcinoma (MCC) is a malignant skin cancer with a 5-year survival rate of approximately 50%. Knowledge of MCC has increased in recent years mostly due to improved diagnosis techniques. In Spain there is lack of information regarding the incidence and tumour characteristics, and the treatment approaches are not standardised. The objective of this study was to provide information of the clinical and epidemiological characteristics of MCC patients in Spain. METHODS: Retrospective, observational study involving 192 patients from 25 Spanish hospitals. Evaluated variables included overall survival and incidence rate of Merkel cell polyomavirus, in patients diagnosed from 2012 to 2016. RESULTS: The Spanish incidence rate was estimated 0.32/100,000 inhabitants/year, with variations according to geographical regions, being slightly higher in areas with greater sunlight exposure. In total, 61.5% of tumours showed expansive growth (progressive growth of the tumour), 78.6% showed localisation in UV-exposed skin. 97.4% of patients were diagnosed by excisional biopsy. Surgery was the first line treatment in 96.6% of patients, radiotherapy in 24.6%, and chemotherapy in 6.3%. These treatments were not mutually exclusive. Median overall survival was 38.3 months (78.4% at 12 months and 60% at 24 months). MCPyV was present in 33.8% of patients. CONCLUSION: The incidence of MCC in Spain is one of the highest in Europe, with a slight predominance in men. The sample has shown that a biopsy is available for diagnosis in most cases. Moreover, the treatment is surgical when the tumour is localized and is associated with lymphadenectomy, and/or it is radiotherapy if widespread.

Congenital hepatic hemangiomas: Clinical, histologic, and genetic correlation.

BACKGROUND: The guide for monitoring and treatment of congenital hepatic hemangiomas (CHH) will depend on the subtype and the postnatal clinical behavior. Our aim is to present a series of CHH and characterize its clinical, histologic and genetic correlation, compared to cutaneous congenital hemangiomas (CCH). MATERIAL AND METHODS: A retrospective review of CHH patients diagnosed between 1991 and 2018 was performed. Clinical, morphological and histological data were analyzed and deep high-throughput sequencing was performed. MAIN RESULTS: Sixteen patients with CHH were included. Five patients were followed up with serial ultrasounds while pharmacological treatment (corticosteroids and propranolol) was decided in five. Surgical resection was performed in five owing to hemorrhage and suspicion of malignancy, and the last patient underwent embolization. Histologic analysis was available in 7 patients and confirmed CHH, showing two different histological patterns that could be associated with the presence of somatic pathogenic variants in GNAQ and/or PIK3CA detected in the genetic testing. Review of 7 samples of CCH revealed some histologic differences compared to CHH. CONCLUSION: CHH resemble its cutaneous homonym with similar clinical behavior. Histologic analysis can differentiate two subgroups while genetic testing can confirm mutations in GNAQ and in PIK3CA in a subset of CHH. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: IV.

Hamartomas and midline anomalies in association with infantile hemangiomas, PHACE, and LUMBAR syndromes.

BACKGROUND/OBJECTIVE: The pathogenesis of infantile hemangiomas (IH), PHACE, and LUMBAR syndromes remains unknown. We aim to describe histopathologic features of midline anomalies associated with IH, including patients with PHACE and LUMBAR syndromes. METHODS: A multicenter retrospective chart review was performed to identify patients with IH, PHACE, and LUMBAR syndrome with histopathologic specimens from sternal or midline anomalies. A total of 18 midline lesions from 13 patients were included. Out of 18, 14 midline lesions underwent both histopathologic and clinical review. Three hamartoma-like chin plaques and one supraumbilical raphe underwent only clinical review. RESULTS: All 13 patients had midline lesions and IH. Histopathologic diagnoses were as follows: rhabdomyomatous mesenchymal hamartoma (3), folliculosebaceous cystic hamartoma (1), fibroepithelial polyp (1), verrucous epidermal hyperplasia with vascular proliferation and fibroplasia (1), congenital midline cervical cleft (1), pericardium with fibrosis (1), fibrous components with increased collagen (1), atrophic skin/membrane (3), angiolipomatous mass with neural components (1), and lipomatous mass (1). Due to the retrospective nature of this study, it was not possible to obtain pathology slides for all midline lesions that had previously been biopsied or resected. We show clinically and histopathologically a new association between PHACE syndrome and rhabdomyomatous mesenchymal hamartoma (RMH), in addition to demonstrating the association between PHACE syndrome and chin hamartomas. We also display histopathologic findings seen in midline lesions resected from LUMBAR patients. CONCLUSION: Rhabdomyomatous mesenchymal hamartoma is thought to be related to aberrations of mesenchymal cells during development; therefore, this may provide clues to the pathogenesis of IH and related syndromes.

Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly.

Generalized lymphatic anomaly (GLA) is a vascular disorder characterized by diffuse or multifocal lymphatic malformations (LMs). The etiology of GLA is poorly understood. We identified four distinct somatic PIK3CA variants (Glu542Lys, Gln546Lys, His1047Arg, and His1047Leu) in tissue samples from five out of nine patients with GLA. These same PIK3CA variants occur in PIK3CA-related overgrowth spectrum and cause hyperactivation of the PI3K-AKT-mTOR pathway. We found that the mTOR inhibitor, rapamycin, prevented lymphatic hyperplasia and dysfunction in mice that expressed an active form of PIK3CA (His1047Arg) in their lymphatics. We also found that rapamycin reduced pain in patients with GLA. In conclusion, we report that somatic activating PIK3CA mutations can cause GLA, and we provide preclinical and clinical evidence to support the use of rapamycin for the treatment of this disabling and deadly disease.

Cutaneous fibrolipomatous hamartoma: Report of 2 cases with retrocalcaneal location.

Precalcaneal congenital fibrolipomatous hamartoma is an underreported benign entity that has been described in the literature under different names. We present two cases of unilateral fibrolipomatous hamartoma (FLH) appearing in a unique location: on the posterior aspect of the foot overlying the heel. We propose the term "FLH of the skin" as a more inclusive and less confusing term for this condition, thus allowing distinction with FLH arising from neural tissue. High-frequency ultrasonography appears to be a useful diagnostic tool that may avoid unnecessary biopsies for this condition.

Notalgia Paresthetica and Multiple Endocrine Neoplasia Syndrome 2A: A Case Report.

Notalgia paresthetica is characterized by a hyperpigmented macular pruritic skin lesion most commonly localized unilaterally in the middle and upper back region. This condition has been reported in association with multiple endocrine neoplasia syndrome type 2A (MEN 2A) in several families; it rarely affects children and it may serve as an early marker of MEN 2A. We report a 9-year-old girl diagnosed with MEN 2A and notalgia paresthetica.

Pulmonary and pleural lymphatic endothelial cells from pediatric, but not adult, patients with Gorham-Stout disease and generalized lymphatic anomaly, show a high proliferation rate.

BACKGROUND: Gorham-Stout disease (OMIM 123880) and generalized lymphatic anomaly are two rare disorders of lymphendothelial growth in which thoracic involvement with chylothorax is a feared complication. Currently it is believed that both disorders are prenatal malformations that progress slowly after birth. Several pharmaceuticals with antiproliferative properties, including interferon-α-2b, rapamycin and propranolol, have however been shown to affect the disease course in some patients. Deeper knowledge of the growth characteristics of these malformations are therefore needed to guide the clinical approach. METHODS: Lymphatic vessels in lung and pleural tissue from both children and adult patients with generalized lymphatic anomaly or Gorham-Stout disease were studied using an immunohistochemical approach, targeting lymphendothelial markers (D2-40/Prox-1) and a proliferation marker (Ki-67). RESULTS: We found significant proliferation and growth in these lesions in pediatric patients but not in adults. Furthermore, the data may suggest that the disease process is at least partly reversible. CONCLUSIONS: These malformations of the lymphatic system proliferate at a significant rate long after birth, which could suggest that the clinical approach for children should be different from adults.

Topical cidofovir to treat high-grade anal intraepithelial neoplasia in HIV-infected patients: a pilot clinical trial.

OBJECTIVE: To evaluate the efficacy of 1% topical cidofovir cream for the treatment of anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals. DESIGN: Single-arm, open-label, pilot clinical trial. METHODS: The study medication was applied intraanally three times per week for 4 weeks. Lesions were assessed with high-resolution anoscopy and biopsy at weeks 12 and 24. The primary endpoint was complete remission (CR) at week 12, defined as clinical and histological remission. We also evaluated partial remission defined as regression to low-grade squamous intraepithelial lesion. RESULTS: We included 17 HIV-infected patients with intraanal HSIL. Median (interquartile range) age was 36 years (28-41), median (interquartile range) CD4 cell count was 545 cells/µl (358-630), and viral load was less than 50  copies/ml in 93.7%. Two patients were lost to follow-up, one of them did not apply treatment. At 12 weeks, in the intention-to-treat population, 10 out of 16 patients [62.5%; 95% confidence interval (CI), 38.2-85.7%] had achieved CR. At 24 weeks, seven of the 10 patients (70%; 95% CI, 47-93%) remained in CR, but two out of 10 patients (20%; 95% CI, 0-40%) presented HSIL. One patient did not attend the visit at 24 weeks. Three patients with persistent HSIL at 12 weeks improved at 24 weeks (partial response in one and CR in two). The mean number of human papillomavirus genotypes decreased from 5.2 to 2.7 at 12 weeks (P = 0.002). Local adverse effects were frequent (81%), although there were no discontinuations because of adverse events. CONCLUSION: One percent topical cidofovir could be an appropriate alternative therapy in HIV-infected patients with anal HSIL. CLINICAL TRIAL: gov unique identifier: NCT01946009.

Trichodysplasia Spinulosa in a 20-Month-Old Girl With a Good Response to Topical Cidofovir 1%.

Trichodysplasia spinulosa (TS) is a rare entity, characterized by a follicular digitate keratosis predominantly affecting the face and variable degrees of hair loss, most severely facial hair, that occurs in immunosuppressed individuals, and is considered to be a viral infection caused by a human polyomavirus, the "TS-associated polyomavirus." Histologically it is characterized by hair follicles with excessive inner root-sheath differentiation and intraepithelial viral inclusions. Correlation of these findings with clinical features is required for diagnosis. Treatment with antiviral agents appears to be the most effective. We report the occurrence of TS in a 20-month-old girl with multivisceral transplantation due to short-bowel syndrome secondary to intestinal atresia and gastroschisis. The patient was treated with cidofovir 1% cream, with significant improvement and without any adverse effects. We describe the youngest patient, to our knowledge, with TS.

Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in men who have sex with men infected with HIV.

Currently, screening for anal high-grade squamous intraepithelial lesions (anal HSIL) relies on anal cytology and high-resolution anoscopy. Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM infected with HIV, in comparison to DNA-HR-HPV and anal cytology. This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, high-resolution anoscopy and histology were analyzed. HR-HPV-DNA detection was performed by means of the CLART® HPV2 assay (GENOMICA S.A.U., Madrid, Spain). E6/E7-mRNA detection of HR-HPV-types 16, 18, 31, 33, and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy lEtoile, France). HR-HPV DNA and HPVE6/E7 mRNA were detected in 82% and 57% of the anal smears respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared to 100%, 31.5%, 55.4%, and 100% for HR-HPV-DNA testing and to 83%, 40.7%, 54.9%, 73.3% of cytology testing. In comparison with the other tests, HPVE6/E7 mRNA testing yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM infected with HIV.

Prevalence of abnormal anal cytology and high-grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with men.

BACKGROUND: The incidence of anal cancer among HIV-infected patients is higher than that in other populations. Anal high-grade squamous intraepithelial lesions are considered precursors to invasive squamous-cell carcinomas and are strongly associated to high-risk human papillomavirus infection. OBJECTIVE: The aim of this study is to determine the prevalence of anal high-grade squamous intraepithelial lesions through screening based on cytology and high-resolution anoscopy with biopsy in a cohort of HIV-infected men who have sex with men. DESIGN: This investigation is an observational cross-sectional cohort study. SETTING: The study was conducted in the HIV unit of a tertiary hospital in Spain. PATIENTS: Three hundred HIV-infected men who have sex with men participated. Physical examination led to a diagnosis of perianal squamous-cell carcinoma and high-grade squamous intraepithelial lesions in 2 patients who were then excluded. INTERVENTIONS: Anal liquid cytology was performed. Patients with cytological abnormalities underwent high-resolution anoscopy and biopsy. MAIN OUTCOME MEASURE: The primary outcome measured was biopsy-proven high-grade squamous intraepithelial lesions. RESULTS: The median age was 41 ± 10.5 years. The mean and nadir CD4 cell counts were 651 ± 205 cells/mm(3) (interquartile range, 438-800) and 273 ± 205 cells/mm(3) (interquartile range, 131-362). High-risk human papillomavirus was detected in 80.9% of patients, and human papillomavirus 16 was detected in 35.9% of patients. The mean number of human papillomavirus genotypes was 4.6 ± 2.9 (CI, 2-6). Anal cytology was abnormal in 40.9% of patients (n = 122/298; interquartile range, 35.4%-46.6%). High-resolution anoscopy and biopsies were performed in 119 patients. The results of histological analyses were as follows: normal, 7.7% (n = 23); condyloma, 4.3% (n = 13); anal intraepithelial neoplasia 1, 5.7% (n = 17); anal intraepithelial neoplasia 2, 14% (n = 42); and anal intraepithelial neoplasia 3, 8% (n = 24). The overall prevalence of high-grade squamous intraepithelial lesions among patients with abnormal cytology was 54% (95% CI, 45.1%-62.8%). A diagnosis of high-grade squamous intraepithelial lesions was associated with human papillomavirus 16 and human papillomavirus 51 infection, and with detection of a higher number of human papillomavirus genotypes. LIMITATIONS: High-resolution anoscopy was only performed in patients with abnormal cytology. CONCLUSIONS: The prevalence of high-risk human papillomavirus infection and high-grade squamous intraepithelial lesions is high in our cohort. Physical examination enabled straightforward diagnosis of perianal high-grade squamous intraepithelial lesions and squamous-cell carcinoma in 2 patients.

Disseminated fusariosis in a pediatric population.

Members of the genus Fusarium are ubiquitous filamentous fungi that can cause disease in immunocompromised patients. We present a case in which the resistance to conventional antifungal therapies led to a fatal outcome.

Cutaneous emboli of atrial myxoma: unusual case report and review of the literature.

Cardiac myxomas are difficult to diagnose, not only because of a lack of specific systemic symptoms but also because, even in those cases presenting with embolic disease, emboli are exceptional. The skin is one of the organs most frequently involved by myxomatous emboli. We report an extraordinary case in which emboli of a cardiac myxoma was present in the skin biopsy, but "camouflaged" among the normal Vater-Pacini corpuscles of the palm of the hand, We also review the existing literature on myxomatous emboli identified in skin biopsies.

Letter: Umbilical basal cell carcinoma in a 21-year-old man: Report of an exceptional case and dermatoscopic evaluation.

We report an exceptional case of umbilical basal cell carcinoma (BCC) in a 21-year-old man, whose correct diagnosis was suggested by dermoscopy during initial complete body mole mapping. Although BCC is a common skin tumor, only 7 cases of BCC arising within the umbilicus have been reported previously. To the best of our knowledge, our patient is unique because of his age, being the youngest case of umbilical BCC described in the literature. Complete examination and digital dermoscopic monitoring let us identify an asymptomatic, nonpigmented papule at the umbilicus. Dermoscopy images revealed signs of superficial ulceration and several types of vascular structures, which gave us the clue for the diagnosis and helped us differentiate it from other lesions such as Spitz nevus or amelanotic melanoma. The diagnosis was confirmed with histopathology after excision and there was no evidence of relapse in the following four years.

Dermoscopic findings and histological correlation of the acral volar pigmented maculae in Laugier-Hunziker syndrome.

Laugier-Hunziker syndrome (LHS) is an acquired, benign, macular hyperpigmentation of the lips and oral mucosa, often associated with pigmentation of the nails. Volar acral maculae on the palms and fingertips of patients affected by LHS are a typical feature of this rare entity. Dermoscopic examination of these maculae has been described in a previous report, in which authors found a parallel-furrow pattern. We describe two cases in which a parallel-ridge pattern (PRP) was found on the dermoscopic examination of the pigmented acral lesions. Histological examination showed increased melanin in basal keratinocytes, which was most prominent in those located at the crista intermedia profunda, that is, in the epidermal rete ridges underlying the surface ridges. In our study, dermoscopic features of the pigmented maculae found on LHS differed from those previously described. In addition, by means of this case report, the histological features of these lesions are described for the first time, showing an excellent correlation with dermoscopy. The reported cases prove that although the PRP is very specific of melanoma, it is also possible to find it in benign lesions. Therefore, we must be familiar with the differential diagnosis of PRP, and take into consideration the clinical context in which we find it. Further studies are needed to increase our knowledge on the histological and dermoscopic features of acral pigmented maculae of LHS.

Dermatoscopic characteristics of acrochordon-like basal cell carcinomas in Gorlin-Goltz syndrome.

BACKGROUND: Gorlin-Goltz syndrome (GGS) is an autosomal-dominant disease characterized by the early onset of multiple basal cell carcinomas (BCCs), among other findings. Clinically, the BCCs may appear as soft pedunculated neoplasms that can be mistaken for true acrochordons. OBJECTIVE: We sought to describe the dermatoscopic characteristics of small acrochordon-like or polypoid BCCs in a child with GGS, and to perform histopathologic correlation. METHODS: Acrochordon-like growths from a child with GGS were studied. Clinical records and digital dermatoscopic images were collected, and excision and histopathologic examination of the most representative lesions were performed. RESULTS: Some acrochordon-like lesions showed specific dermatoscopic criteria for BCC, including multiple blue-gray globules and arborizing telangiectasia. Other polypoid lesions, especially the smaller ones, exhibited characteristics that suggested BCC, such as isolated blue-gray globules, small blue-gray ovoid nests, and fine elongated telangiectases. LIMITATIONS: Conclusions are limited by the small sample size. CONCLUSION: Dermatoscopy may be a useful diagnostic tool to analyze acrochordon-like lesions in children and to facilitate early diagnosis and treatment of BCCs in patients with GGS.

A conventional, inactivated oil emulsion vaccine suppresses shedding and prevents viral meat colonisation in commercial (Pekin) ducks challenged with HPAI H5N1.

The ongoing H5N1 epidemic is currently affecting a number of avian species, including waterfowl. These birds appear to have an important role as reservoirs of infection and comprehensive data on the efficacy of vaccination is currently lacking. The present paper reports the effect of a two dose vaccination programme with a conventional inactivated product on infection, lateral spread, shedding and presence of virus in commodities such as meat and viscera of Pekin ducks. Vaccination of this species appears to be efficacious in suppressing viral shedding, and preventing viraemia and lateral spread of infection to unvaccinated and vaccinated Pekin ducks.

[Granuloma from liquid silicone]. / Granuloma por silicona líquida.

In recent years, the demand for cosmetic interventions to augment soft tissue by injecting different substances has increased, due to their apparent innocuity. However, these procedures are not free from adverse reactions, such as the formation of foreign body granulomas, a phenomenon described in literature with most of the materials used. We report the case of a female patient with inflammatory lesions of the face, whose diagnosis was made after the histopathological study, which revealed a granuloma caused by liquid silicone.