International expert recommendations on image acquisition for in vivo reflectance confocal microscopy of cutaneous tumors.

BACKGROUND: No international recommendations exist for a minimum imaging requirement per lesion using reflectance confocal microscopy (RCM). This may be beneficial given the increasing use of remote RCM interpretation internationally. OBJECTIVE: To develop international expert recommendations for image acquisition using tissue-coupled RCM for diagnosis of cutaneous tumors. METHODS: Using a modified Delphi approach, a core group developed the scope and drafted initial recommendations before circulation to a larger group, the Cutaneous Imaging Expert Resource Group of the American Academy of Dermatology. Each review round consisted of a period of open comment, followed by revisions. RESULTS: The recommendations were developed after 5 alternating rounds of review among the core group and the Cutaneous Imaging Expert Resource Group. These were divided into subsections of imaging personnel, recommended lesion criteria, clinical and lesion information to be provided, lesion preparation, image acquisition, mosaic cube settings, and additional captures based on lesion characteristics and suspected diagnosis. LIMITATIONS: The current recommendations are limited to tissue-coupled RCM for diagnosis of cutaneous tumors. It is one component of the larger picture of quality assurance and will require ongoing review. CONCLUSIONS: These recommendations serve as a resource to facilitate quality assurance, economical use of time, accurate diagnosis, and international collaboration.

Superficial Angiomyxoma of Axilla: A Case Report.

Superficial angiomyxomas of the skin are rare benign cutaneous tumors of soft tissue composed of myxoid matrix and thin-walled blood vessels. They can be sporadic or develop in conjunction with the Carney complex. These tumors have a predilection for the trunk, lower limbs, head, neck, and genitalia. Herein, we report a case of superficial angiomyxoma of the axilla in a 42-year-old man. The pedunculated polypoidal mass showed a maximum diameter of 4.5 cm and intra- and extra-lesional vascularity on Doppler, and the histopathology report was suggestive of myxoid matrix with scattered bland stellate and spindle cells and long thin-walled branching blood vessels and inflammatory infiltrate consisting of mainly neutrophils. Smooth muscle actin (SMA), S100, and desmin were found to be negative on immunohistochemistry, but CD34 was discovered to be positive. It was possible to make the diagnosis of superficial angiomyxoma using these histological and immunohistochemical characteristics. Wide local excision, being the preferred treatment, was performed, and the patient was followed up for six months with no signs of recurrence.

Eyelid atypical fibroxanthoma: a rare challenging entity.

Atypical fibroxanthoma (AFX) is a rare neoplasm, with a limited number of cases reported in the periocular region. In this case report, we detail a 63-year-old woman who presented with a polypoid, exophytic lesion on her right upper eyelid that had been progressing for a year. The lesion was meticulously excised with security margins and reconstructed using a glabellar flap. Following a thorough microscopic and immunohistochemical analysis, AFX was diagnosed. Despite its sometimes clinical and histological benign appearance, AFX is classified as a malignant neoplasm; however, it carries an excellent prognosis with low metastasis and recurrence rates. Complete excision with safety margins is essential and an adequate post-operative surveillance is recommended. Owing to its rarity, ophthalmologists should remain vigilant and include AFX in their differential diagnosis, as the tumor's benign appearance may lead to misdiagnosis of this malignant entity.

Eccrine Porocarcinoma: A Review of the Literature.

Eccrine porocarcinoma (EPC) constitutes a rare malignant adnexal tumor, which accounts for about 0.005-0.01% of all cutaneous malignancies. It may develop de novo or arise from an eccrine poroma, after a latency period of years or even decades. Accumulating data suggest that specific oncogenic drivers and signaling pathways may be implicated in its tumorigenesis, while recent data have demonstrated a high overall mutation rate attributed to UV exposure. Diagnosis may be challenging and should rely on the combination of clinical, dermoscopical, histopathological and immunohistochemical findings. The literature is controversial regarding tumor behavior and prognosis and, therefore, there is no consensus on its surgical management, utility of lymph-node biopsy and further adjuvant or systemic treatment. However, recent advances in tumorigenesis of EPC may aid in the development of novel treatment strategies, which could improve survival of advanced or metastatic disease, such as immunotherapy. This review presents an update of the epidemiology, pathogenesis and clinical presentation of EPC and summarizes current data on diagnostic evaluation and management of this rare cutaneous malignancy.

Diagnosis and differential diagnosis of dermatofibrosarcoma protuberans: Utility of high-resolution dynamic contrast-enhanced (DCE) MRI.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a kind of low-grade malignant spindle cell neoplasm, the diagnosis, and treatment, which have markedly attracted clinicians' attention for its repeated recurrence. High-resolution magnetic resonance imaging (HR-MRI) has shown unique capabilities in diagnosis of various cutaneous tumors. MATERIALS AND METHODS: Data of 29 patients with clinically suspected DFSPs and undergoing dynamic contrast-enhanced (DCE) HR-MRI preoperatively were prospectively collected. The HR-MRI qualitative features were evaluated and compared. The DCE-associated quantitative parameters and the time-signal intensity curve (TIC) types were provided using DCE sequences. RESULTS: A total of 7 DFSPs, nine dermatofibromas (DF, including four cases of cellular variant [CDF]), 12 keloids, and one nodular fasciitis were enrolled. DFSP showed the largest major diameter and the deepest depth. Five DFSPs (71.4%) showed ill-defined margins as well as infiltration of peripheral adipose. All DFSPs showed irregular shape. Most DFSPs presented hyperintensity on T2 WI (71.4%) and iso-intensity on T1 WI (85.7%). Six cases (85.7%) had significant enhancement, and six cases (85.7%) had homogeneous enhancement. There were significant differences of Ktrans , Kep , Ve and iAUC values among DFSPs, DFs, and keloids, and DFSP had the highest values for these parameters. Six DFSPs (85.7%) and four CDFs (100%) showed type-III TICs, while the other lesions showed type-Ⅰor type-Ⅱ TICs. CONCLUSIONS: DCE-HR-MRI could show the growth characteristics of DFSPs, which was of great value for the diagnosis and differential diagnosis of DFSPs and was helpful for the determination of treatment options, thereby to improve the prognosis of patients.

Cutaneous Vascular Neoplasms of Uncertain Biological Behavior.

Neoplasms of uncertain biological behavior present physicians with a genuine conundrum in practice. Cutaneous vascular neoplasms within this category are exceedingly rare, possessing significant gaps and uncertainty in many facets of clinical practice. Firstly, lesions were selected for review based on their categorization as indeterminate behavior, indicating the potential for local recurrence and rarely metastasize. After identification of the target lesions, a comprehensive review of the literature using national databases produced several landmark studies and case series regarding these neoplasms. Limiting the review to only cutaneous limited tumors narrowed the pool of studies; however, quite a large sum of papers remained. Examination of each paper yielded beneficial results on diagnosing, effective treatments, follow-up findings, and prognosis for each indeterminate lesion discussed. Overall, the literature search combined the molecular, histologic, immunohistochemical, surgical strategies to develop an up-to-date and comprehensive framework to guide physicians when encountering such lesions. The tumors reviewed include: kaposiform hemangioendothelioma, endovascular papillary angioendothelioma, pseudomyogenic hemangioendothelioma, retiform hemangioendothelioma, epithelioid hemangioendothelioma, and composite hemangioendothelioma.

Pacinian corpuscle hyperplasia: A review of the literature.

OBJECTIVE: Pacinian corpuscle hyperplasia typically presents as a tender nodule on the volar aspect of the palm or digit, often after trauma. Histologically, it presents as one to multiple normal-sized to enlarged Pacinian corpuscles in the deep dermis or subcutaneous adipose tissue. Given its rarity, its pathogenesis is debated and nomenclature is poorly defined. Herein, we present a case of Pacinian corpuscle hyperplasia and review the current literature. METHODS: A literature review was conducted using PubMed with the following search terms: Pacinian corpuscle hyperplasia, Pacinian corpuscle neuroma, Pacinioma, Pacinian corpuscle hypertrophy, and heterotopic Pacinian corpuscles. All case reports and case series were reviewed for histopathologic evidence of true Pacinian corpuscle hyperplasia. Cadaveric studies, cases without true Pacinian corpuscles, and noncutaneous cases were excluded from our analysis. RESULTS: Sixty patients with Pacinian corpuscle hyperplasia of the hands and feet (65 cases, some with >1 location) were reviewed. The mean age of presentation was 49.5 years, and women accounted for 60% of cases. Pain was the most commonly reported symptom (55 of 65 cases; 84.6%). Forty-five cases (69.2%) were localized to a digit, most commonly the second digit (17 of 65 cases; 26.2%), and 18 of 65 cases (27.6%) affected the palm, primarily the distal palm. Surgical excision was curative in 50 of 65 cases (76.9%). CONCLUSION: Although relatively uncommon, Pacinian corpuscle hyperplasia should be considered in the differential diagnosis of a tender nodule on the digit or distal palm, particularly after trauma.

Emerging role of human polyomaviruses 6 and 7 in human cancers.

BACKGROUND: Currently 12 human polyomaviruses (HPyVs) have been identified, 6 of which have been associated with human diseases, including cancer. The discovery of the Merkel cell polyomavirus and its role in the etiopathogenesis in the majority of Merkel cell carcinomas has drawn significant attention, also to other novel HPyVs. In 2010, HPyV6 and HPyV7 were identified in healthy skin swabs. Ever since it has been speculated that they might contribute to the etiopathogenesis of skin and non-cutaneous human cancers. MAIN BODY: Here we comprehensively reviewed and summarized the current evidence potentially indicating an involvement of HPyV6 and HPyV7 in the etiopathogenesis of neoplastic human diseases. The seroprevalence of both HPyV6 and 7 is high in a normal population and increases with age. In skin cancer tissues, HPyV6- DNA was far more often prevalent than HPyV7 in contrast to cancers of other anatomic sites, in which HPyV7 DNA was more frequently detected. CONCLUSION: It is remarkable to find that the detection rate of HPyV6-DNA in tissues of skin malignancies is higher than HPyV7-DNA and may indicate a role of HPyV6 in the etiopathogenesis of the respected skin cancers. However, the sheer presence of viral DNA is not enough to prove a role in the etiopathogenesis of these cancers.

Systematic review of Mohs micrographic surgery in children: Identifying challenges and practical considerations for successful application.

BACKGROUND: Few data exist to guide the application of Mohs micrographic surgery (MMS) in the pediatric population. OBJECTIVE: We sought to summarize the clinical characteristics of children undergoing MMS, identify challenges that limit the use of MMS in this population, and examine how these challenges can be overcome. METHODS: A systematic review of PubMed and EMBASE, from inception of databases to November 2, 2019, identified all cases of pediatric skin lesions treated with MMS. RESULTS: A total of 111 patients were included. The median patient age was 11 years (range 6 weeks to 17 years). The most commonly treated tumor was dermatofibrosarcoma protuberans (n = 62), followed by basal cell carcinoma (n = 30). The most common location was the head and neck (n = 34), followed by the trunk (n = 28) and the extremities (n = 23). The most commonly cited challenges in the application of MMS in children included patient cooperation, concerns for the safety of prolonged general anesthesia, availability of a MMS service in the pediatric setting, and access to a histopathology laboratory experienced in MMS sectioning. LIMITATIONS: Many articles did not report specific patient characteristics. CONCLUSION: Multiple obstacles limit the application of MMS in pediatric patients. This review describes practical methods to circumvent these obstacles to facilitate the appropriate use of MMS in children.

Treatment of Infiltrative Superficial Tumors in Awake Standing Horses Using Novel High-Frequency Pulsed Electrical Fields.

Irreversible electroporation is a proven ablation modality for local ablation of soft tissue tumors in animals and humans. However, the strong muscle contractions associated with the electrical impulses (duration, 50-100 µs) requires the use of general anesthesia and, in most situations, application of neuromuscular blockade. As such, this technology is not used in an outpatient setting for ablating common cutaneous tumors (e.g., squamous cell carcinoma or melanoma) in humans or animals. Recently, high-frequency irreversible electroporation (H-FIRE) technology has been developed to enable electroporation of tumors without stimulation of nearby skeletal muscle. H-FIRE administers bursts of electrical pulses (duration, 0.5-2 µs) through bipolar electrodes placed in tumor parenchyma. We hypothesized that H-FIRE could be used to safely ablate superficial tumors in standing, awake horses without the need for general anesthesia. Here, we describe the treatment of superficial tumors in five horses using this novel ablation therapy without the need for general anesthesia. In each case, H-FIRE therapy predictably ablated tumor volume. All patients tolerated the procedure, no complications developed, and veterinary personnel safety was maintained. The H-FIRE treatment may be useful for treatment in veterinary and human patients in an outpatient setting without the need for hospitalization, general anesthesia, and advanced monitoring techniques.

Caracterização anatomopatológica e imuno-histoquímica dos tumores das glândulas cutâneas em cães / Anatomopathological and immunohistochemical characterization of skin gland tumors in dogs

O presente estudo objetivou caracterizar os aspectos anatomopatológicos e imuno-histoquímicos dos tumores das glândulas cutâneas em cães. A caracterização morfológica seguiu a classificação atualizada da Organização Mundial de Saúde. Para a caracterização imuno-histoquímica, utilizaram-se anticorpos monoclonais primários anti-citoqueratina 14 (CK14), vimentina, p63, calponina, EGFR e Ki-67. Dos animais examinados, 66,67% (18/27) eram machos e 33,33% (9/27) fêmeas, 21 tinham raça definida e seis eram sem raça definida (SRD), com idade variando entre sete e 15 anos. Dos tumores caracterizados, 40,74% eram hepatoides (11/27), 29,63% sebáceos (8/27), 25,92% apócrinos (7/27) e 3,70% meibômio (1/27). Os tumores malignos representaram 55,56%, e os benignos 44,44%. Com esses resultados, foi possível demonstrar que os tumores das glândulas cutâneas em cães são frequentes, sem predileção por raça, sexo e com idade superior ou igual a sete anos. Os anticorpos CK 14, p63, vimentina e EGFR foram imunoexpressos nas células basais, células de diferenciação sebácea dos tumores hepatoides e de meibômio e células mioepiteliais. Entretanto, a vimentina e o EGFR não demonstraram imunomarcação para os tumores sebáceos. A calponina foi um bom marcador para as células mioepiteliais. O índice de Ki-67 foi mais acentuado nos tumores malignos em relação aos benignos. No entanto, estudos futuros utilizando maior número de casos se fazem necessários.(AU)

The present study aimed to characterize the anatomopathological and immunohistochemical aspects of cutaneous glandular tumors in dogs. Tumours were diagnosed according to the WHO criteria for canine skin neoplasms. For the immunohistochemical characterization, the primary monoclonal antibodies anti-cytokeratin 14 (CK14), vimentin, p63, calponin, EGFR and Ki-67 were used. Males were 66.67% (18/27) and females 33.33% (9/27), 21 had a defined race and 6 were mixed breed, with ages varying from 7 to 15 years. The tumors characterized were 40.74% hepatoid (11/27), 29.63% sebaceous (8/27), 25.92% apocrine (7/27) and 3.70% Meibômio (1/27). Malignant tumors accounted for 55.56% and benign tumors 44.44%. With these results it was possible to demonstrate that tumors of cutaneous glands in dogs are frequent, with no predilection for race, sex and with an age ≥ seven years. The CK 14 antibodies, p63, vimentin, and EGFR were imunoexpressed in the basal cells of the sebaceous cell differentiation and Meibomian hepatoides tumors and myoepithelial to cells. However, vimentin and EGFR did not demonstrate immunostaining for sebaceous tumors. Calponin was a good marker for myoepithelial cells. The Ki-67 index was more pronounced in malignant tumors compared to benign tumors. However, more studies are needed mainly using a higher number of tumors.(AU)

Evaluation of matrix metalloproteinases (MMP)-2 and MMP-9 activity in serum and biochemical and hematological parameters in spontaneous canine cutaneous tumors before and after surgical treatment.

Recently, matrix metalloproteinases (MMP), in particular the gelatinases MMP-2 and MMP-9, generally considered as tumor markers for clinical applications. A longitudinal 2-years follow-up survey was performed on dogs with cutaneous tumor. Serum samples were obtained from 22 dogs with different cutaneous tumors and 22 health dogs at the time of surgery and one month, three months and one year after surgery. Gelatin zymography, hematological and biochemical assessment were performed for all serum samples. The serum alkaline phosphatase activity in dogs with malignant tumors was significantly higher than that in dogs with benign tumors and control cases. Latent forms of MMP-2 and MMP-9 were detected in all of the tumor cases. Gelatin zymography showed active form of MMP-9 in 12 cases (three benign and nine malignant tumors) and active form of MMP-2 in one fibrosarcoma case. Serum activity of active-MMP-9 and total MMP-9 was significantly higher in dogs with cutaneous tumors than those in controls. Tumor cases had higher serum activity of active-MMP-9 rather than controls. MMPs and alkaline phosphatase activities in serum were decreased significantly after surgery. Only one case with perianal gland adenoma showed recurrence of tumor four months after surgery in which active form of MMP-9 had identified one month before recurrence. According to the findings, it will be useful to measure ALP, MMP-2 and MMP-9 activities in the serum of dogs with cutaneous tumor for determination of tumor behavior before surgical treatment.

Surgical approaches in neck dissection: Comparing functional, oncologic and aesthetic aspects of transverse cervicotomy to Paul André's approach.

BACKGROUND: Surgical approaches in neck dissection: comparing functional, oncologic and aesthetic aspects of transverse cervicotomy to Paul André's approach. METHODS: This single-center retrospective study compares a new transverse incision for cervicotomy to the classical approach described by Paul André in neck dissections. The evaluation criteria were: number of lymph nodes analyzed, operative time, complications, patient satisfaction and aesthetic aspects of the scar. RESULTS: A total of 34 patients were included in this study, from September 2009 until January 2015. The number of lymph nodes analyzed is not affected by this new approach compared to the classical one (P=0.9). The scar has a significantly more discreet appearance in the transverse cervicotomy group (P=0.023) likewise; patient satisfaction is higher in this group (P=0.006). CONCLUSIONS: Aesthetic and functional impairment can be reduced using this new transverse cervical approach hidden in the natural creases of the neck described by Langer.

Clinical Efficacy of Romidepsin in Tumor Stage and Folliculotropic Mycosis Fungoides.

BACKGROUND: Tumor stage and folliculotropic mycosis fungoides are uncommon subtypes of cutaneous T-cell lymphoma (CTCL) with an aggressive disease course. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with CTCL who have received ≥ 1 previous systemic therapy. In the present study, we examined the efficacy and safety of romidepsin in patients from the pivotal, single-arm, open-label, phase II study of relapsed or refractory CTCL with cutaneous tumors and/or folliculotropic disease involvement. MATERIALS AND METHODS: Patients with CTCL who had received ≥ 1 previous systemic therapy received romidepsin at 14 mg/m2 on days 1, 8, and 15 of 28-day cycles. Responses were determined by a composite endpoint (assessments of the skin, blood, and lymph nodes). Patients with cutaneous tumors and/or folliculotropic disease involvement were identified by review of diagnosis and histology reports. RESULTS: The objective response rate to romidepsin was 45% in patients with cutaneous tumors (n = 20) and 60% in patients with folliculotropic disease involvement (n = 10). CONCLUSION: Romidepsin is active in subtypes of CTCL with less favorable outcomes, such as tumor stage and folliculotropic mycosis fungoides.

[Sporadic cutaneous lymphosarcoma of T-cell origin with involvement of lymph nodes and internal organs in a Holstein cow]. / Sporadische kutane T-Zell-Leukose mit Beteiligung von Lymphknoten und inneren Organen bei einer Holstein-Kuh.

Sporadic lymphosarcomas in adult cattle are rare entities with an unknown etiology. This case report describes the course of the disease in a 3.5-year-old cow of the breed German Holstein, which was presented to the veterinarian due to multifocal nodular skin lesions. Several superficial lymph nodes (Lymphonodi mandibulares, parotidei and mammariae) were enlarged, had a tight-elastic consistency and were freely movable. The histopathological and immunohistochemical examination of skin biopsies showed the presence of multifocal cutaneous T-cell lymphosarcomas consistent with a skin leukosis. Bovine leukemia virus infection was excluded by serological investigation of a milk sample and virological examination of a tissue sample, respectively. Seven weeks after the first clinical examination, the cow deteriorated rapidly and was euthanized. A post mortem examination revealed the presence of neoplastic cells within lymph nodes (all superficial lymph nodes of the carcass and Lymphonodi pulmonales), kidney and lungs as well as a liver rupture. Additionally, an overview of the case reports of sporadic bovine cutaneous lymphosarcomas published during the previous 15 years will be provided. The legal background for a further utilization of affected animals for milk and meat production will be discussed. This case report illustrates that sporadic bovine leukosis represents an important differential diagnosis for viral-, bacterial- and parasitic-induced skin lesions and enlargement of lymph nodes in adult cattle.

Angioleiomioma cavernoso cutáneo: Presentación de un caso / Cutaneous cavernous angioleiomyoma: A case report

El angioleiomioma es una neoplasia cutánea rara, benigna, que deriva de las células musculares lisas de los vasos sanguíneos. Se presenta habitualmente en los miembros inferiores de mujeres de edad mediana, como un tumor doloroso. El subtipo histológico cavernoso es poco frecuente. El tratamiento de elección es la extirpación quirúrgica de la lesión. Presentamos el caso de una paciente con un angioleiomioma cavernoso plantar izquierdo.

Angioleiomyoma is a rare, benign skin neoplasia derived from smooth muscle cells of blood vessels. It usually occurs in the lower limbs of middle-aged women as a painful tumor, palms and soles. The cavernous histological subtype is unusual. The treatment of choice is surgical removal of the lesion. We present a case of a patient with a left cavernous angioleiomyoma planting.

Angioleiomioma cavernoso cutáneo: Presentación de un caso / Cutaneous cavernous angioleiomyoma: A case report

El angioleiomioma es una neoplasia cutánea rara, benigna, que deriva de las células musculares lisas de los vasos sanguíneos. Se presenta habitualmente en los miembros inferiores de mujeres de edad mediana, como un tumor doloroso. El subtipo histológico cavernoso es poco frecuente. El tratamiento de elección es la extirpación quirúrgica de la lesión. Presentamos el caso de una paciente con un angioleiomioma cavernoso plantar izquierdo.(AU)

Angioleiomyoma is a rare, benign skin neoplasia derived from smooth muscle cells of blood vessels. It usually occurs in the lower limbs of middle-aged women as a painful tumor, palms and soles. The cavernous histological subtype is unusual. The treatment of choice is surgical removal of the lesion. We present a case of a patient with a left cavernous angioleiomyoma planting.(AU)

The vascular marker CD31 also highlights histiocytes and histiocyte-like cells within cutaneous tumors.

OBJECTIVES: While useful in diagnosing angiosarcomas, CD31 can also highlight histiocytes within soft tissue tumors and lead to errors in diagnosis. We sought to determine how often CD31 highlights cutaneous histiocytomas and histiocytoma mimics. METHODS: We examined eight epithelioid cell histiocytomas (ECHs), 12 xanthogranulomas (XGs), nine cases of Langerhans cell histiocytosis (LCH), eight reticulohistiocytomas, 11 xanthomas, 29 atypical fibroxanthomas, nine granular cell tumors, four cases of angiolymphoid hyperplasia with eosinophilia, nine intradermal Spitz nevi, and nine angiosarcomas with antibodies directed against CD31, CD34, CD163, and factor VIII. RESULTS: CD31 marked cells in three of 12 XGs, four of nine cases of LCH, one of eight reticulohistiocytomas, one of 11 xanthomas, 10 of 29 atypical fibroxanthomas, four of four cases of angiolymphoid hyperplasia with eosinophilia, nine of nine angiosarcomas, zero of nine granular cell tumors, and zero of eight ECHs. CD34 and factor VIII were negative in all nonvascular cases. CONCLUSIONS: Our results indicate that CD31 can mark lesional cells and imitate vascular tumors in cutaneous histiocytomas and histiocytoma mimics, an error that can be avoided by using a panel of antibodies.