SOX10-Internal Tandem Duplications and PLAG1 or HMGA2 Fusions Segregate Eccrine-Type and Apocrine-Type Cutaneous Mixed Tumors.

Cutaneous mixed tumors exhibit a wide morphologic diversity and are currently classified into apocrine and eccrine types based on their morphologic differentiation. Some cases of apocrine-type cutaneous mixed tumors (ACMT), namely, hyaline cell-rich apocrine cutaneous mixed tumors (HCR-ACMT) show a prominent or exclusive plasmacytoid myoepithelial component. Although recurrent fusions of PLAG1 have been observed in ACMT, the oncogenic driver of eccrine-type cutaneous mixed tumors (ECMT) is still unknown. The aim of the study was to provide a comprehensive morphologic, immunohistochemical, and molecular characterization of these tumors. Forty-one cases were included in this study: 28 cases of ACMT/HCR-ACMT and 13 cases of ECMT. After morphologic and immunohistochemical characterization, all specimens were analyzed by RNA sequencing. By immunohistochemistry, all cases showed expression of SOX10, but only ACMT/HCR-ACMT showed expression of PLAG1 and HMGA2. RNA sequencing confirmed the presence of recurrent fusion of PLAG1 or HMGA2 in all cases of ACMT/HCR-ACMT, with a perfect correlation with PLAG1/HMGA2 immunohistochemical status, and revealed internal tandem duplications of SOX10 (SOX10-ITD) in all cases of ECMT. Although TRPS1::PLAG1 was the most frequent fusion, HMGA2::WIF1 and HMGA2::NFIB were detected in ACMT cases. Clustering analysis based on gene expression profiling of 110 tumors, including numerous histotypes, showed that ECMT formed a distinct group compared with all other tumors. ACMT, HCR-ACMT, and salivary gland pleomorphic adenoma clustered together, whereas myoepithelioma with fusions of EWSR1, FUS, PBX1, PBX3, POU5F1, and KLF17 formed another cluster. Follow-up showed no evidence of disease in 23 cases across all 3 tumor types. In conclusion, our study demonstrated for the first time SOX10-ITD in ECMT and HMGA2 fusions in ACMT and further refined the prevalence of PLAG1 fusions in ACMT. Clustering analyses revealed the transcriptomic distance between these different tumors, especially in the heterogenous group of myoepitheliomas.

[The most common benign cutaneous neoplasms of the epidermis and appendages and their treatment]. / Häufigste gutartige Hauttumoren der Epidermis, ihrer Adnexe und deren Behandlung.

Benign cutaneous neoplasms are well defined histologically with absence of all of the following features: architectural disorder, necrosis, cytologic atypia, and atypical mitotic figures. The clinical appearance of any neoplasm is a very important diagnostic factor. The classification of the lesion determines the therapeutic options. This article summarizes the clinical aspects and treatments of the most common benign tumors of the epidermis and its appendages.

Cutaneous pleomorphic adenoma of the periocular region - a case series.

Mixed tumour of the skin is a rare entity also known as chondroid syringoma and pleomorphic adenoma. These usually present as slow-growing skin nodules with a smooth surface, clear boundaries, and no ulceration. Case series exist describing pleomorphic adenomas in the periocular region including the lids and orbit, separate to the more familiar lacrimal gland pleomorphic adenoma. These may arise from accessory or ectopic lacrimal gland tissue but in the eyelids are more likely to arise from sweat glands in the skin. Histopathological analysis of these lesions is important to identify complete excision, minimising recurrences and in identifying rare but potential malignant transformation. We describe the clinical features and outcomes in three cases of pleomorphic adenoma with two at the medial canthus (including one recurrence) and one in the brow region.

An atypical chondroid syringoma with malignant degeneration: Utility of comparative genomic hybridization in confirming the diagnosis.

Chondroid syringoma (CS) represents the cutaneous counterpart of mixed tumor (pleomorphic adenoma) of salivary glands. Definitive diagnosis is made on histopathology and is based on the presence of characteristic epithelial and stromal components. We report a case of an atypical CS arising on the extremity of an elderly male patient. Histomorphologic features of necrosis and cellular atypia raised suspicion for malignant degeneration, an exceptionally rare circumstance in this context. To further support the diagnosis of malignancy, array comparative genomic hybridization was performed from both low and higher grade areas of the tumor. Both regions demonstrated multiple copy number gains and losses, with additional loss of q7p (TP53), loss of 19p, and loss of heterozygosity on16q demonstrated in the more atypical foci. To our knowledge, this is the first case description of malignant degeneration of a CS with correlative microarray analysis. The findings in this case may prove useful in confirming the diagnosis in future ambiguous cases.

Clinical characteristics and pathological depths of syringomas in 94 Korean patients.

BACKGROUND: Syringoma is a common benign tumor with eccrine origin that typically occurs on the face of middle-aged women. Laser ablation with CO2 laser or Er:YAG laser has been widely used in the clinical field, often leading to scars due to its deep location. This study aimed to investigate clinical characteristics and pathological depths of the lesions in syringoma patients. MATERIALS AND METHODS: Syringoma patients, pathologically confirmed at Samsung medical center (Seoul, Korea) from January 1996 to March 2019, were analyzed. Clinical characteristics such as the location of lesion, age, and sex, and pathological depths of the lesions were investigated, and univariable and multivariable analyses were done for these factors. RESULTS: Of total 94 syringomas, 17.0% were located on periocular area, 10.6% on forehead, 34.0% on head and neck areas excluding periocular area and forehead, and 38.3% on trunk and extremities. The mean depth of syringoma from the surface including stratum corneum to the deepest stromal location was 1174.14 ± 1142.95 µm for periocular area, 1055.93 ± 247.76 µm for forehead, 1488.06 ± 1217.36 µm for other areas of head and neck including scalp, and 1169.53 ± 349.2 for the lesions located at trunk and extremities including external genitalia. No significant correlation was observed from univariable analysis and multivariable analysis by age, sex, and site of lesion. CONCLUSION: Our findings offer valuable information of the mean depth of syringoma at different sites, which can be taken into consideration for successful treatment without adverse events such as scarring.

In vivo reflectance confocal microscopy for evaluating seborrheic keratosis, verruca plana, syringoma and lichen nitidus.

BACKGROUND: In clinical, common facial papule dermatosis such as seborrheic keratosis (SK), verruca plana (VP), syringoma and lichen nitidus (LN) is often misdiagnosed. Summarizing in vivo reflectance confocal microscopy (RCM) features of the facial papule dermatosis is helpful in the diagnosis of ambiguous lesions. The purpose of this study was to evaluate the features of SK, VP, syringoma, and LN in RCM. METHODS: We recruited 144 patients referred for unequivocal facial papule dermatosis including 60 patients with SK, 60 patients with VP, 10 patients with syringoma, and 14 patients with LN. The RCM images were evaluated at the epidermis, the dermoepidermal junction, and the dermis from both papule lesions and normal skin. RESULTS: In the epidermis, the cerebriform shape was the main RCM characteristic of SK and the "petal-like" structure was the main RCM characteristic of VP. In the dermoepidermal junction, the RCM features we found were as follows: For SK, the bright dermal papillary rings, the abnormal dermal papilla and the looped vessels were also observed at the abnormal dermal papilla. For VP, the bright dermal papillary rings and the point-like blood vessels were also observed at the round dermal papills. For LN, the round, enlarged, well-circumscribed dermal papillae and the enlarged dermal papillaes were heavily laden with individual highly refractive cells. In the dermis, RCM examination revealed brightly refractile teratogenous sweat tube, designing variably visible bright "moon" structures in all syringoma patients. CONCLUSION: Considering our results, RCM may be useful to non-invasively discriminate SK, VP, syringoma and LN in vivo.

Generalized Eruptive Syringoma in a Nigerian Woman: A Case Report and a Brief Literature Review.

Generalized eruptive syringomas are a very rare variant of syringoma which appear on the chest, neck, abdomen, upper and lower arms, thighs, legs and back. They often affect adolescent or post-adolescent females, although cases have been described in children and older adults. Generalized eruptive syringomas are mostly sporadic but familial cases, and those associated with eczematous skin conditions, solid organ transplants, renal cell carcinoma and some genodermatoses have also been reported. Although eruptive syringomas may resemble cutaneous mastocytosis, disseminated granuloma annulare, eruptive xanthomata, steatocystoma multiplex, eruptive velus hair syndrome, verruca plana and other skin conditions clinically, the histological appearance characterized by upper dermal epithelial cords with a tendency to ductule formation and tadpole extension of outer epithelial layer is diagnostic. We report the case of a 20-year-old Nigerian woman with generalized eruptive syringoma.

Benign chondroid syringoma of the orbit: an atypical location.

A 31-year-old male with no known medical illness presented with painless left eye protrusion for the past 2 years. Radiographic features were of an extraconal superior orbital mass with no invasion of adjacent structures. The patient underwent an excisional biopsy of the left superior extraconal mass a week later. The histopathological examination revealed a well-circumscribed lobulated mass with chondroid and myxoid stroma enveloping benign bland-appearing epithelial and myoepithelial cells. These pathological features were consistent with benign chondroid syringoma of the orbit. The patient had an uneventful recovery with no active ocular complaint post-operatively.Despite chondroid syringoma of the orbit being a rare tumour, it should be considered in the differential diagnosis of periorbital masses. Excision of the tumour remains the treatment of choice with histopathological examination as the gold standard of diagnosis. Regular follow-up is warranted in view of possible local recurrence or metastasis.

Treatment of a case with giant eyelid syringomas.

He had a history of multiple asymptomatic flesh-colored papules, which had slowly increased in number and coalesced into plaques, on both upper and lower eyelids. Some of the plaques were giant and mostly coalescent in nature. We excised surgically the giant plaques which were approximately 1.5-2 cm in diameter symmetrically from upper and lower eylids and the remaining plaques were left to be treated with cauterization. Histopathological examination revealed syringoma. Both of the eyelids were observed to have a cosmetically adequate appearence after the surgical intervention.

Comparison of microinsulated needle radiofrequency and carbon dioxide laser ablation for the treatment of syringoma.

Syringoma is a benign adnexal tumor originating from the intradermal eccrine ducts and predominantly occurs in women at puberty or later in life. We present a case of a 30-year-old woman with a 2-year history of syringoma on her neck and axillar region. She was treated with two devices in a split manner. The right-sided lesions of the neck were treated with one session of 10,600-nm carbon dioxide (CO2 ) laser ablation. The left-sided lesions were treated with microinsulated needle radiofrequency (RF) three times. After treatment, the lesions treated with CO2 showed hypertrophic scar formation, but the other side lesions treated with microinsulated needle RF showed a marked reduction in the size and number of lesions, without any adverse effects such as scarring and hyperpigmentation related to epidermal damage. The treatment of syringoma with microinsulated needle RF, which is insulated at the point of epidermal contact, results in good cosmetic outcomes. Syringoma, microinsulated needle RF, CO2 laser.

Local recurrence of cutaneous mixed tumor (chondroid syringoma) as malignant mixed tumor of the thumb 20 years after initial diagnosis.

Benign cutaneous mixed tumor (chondroid syringoma) is the cutaneous counterpart of the benign mixed tumor (pleomorphic adenoma) of salivary glands, consisting of both epithelial and mesenchymal elements. The incidence of cutaneous mixed tumor is rare, composing <0.01% of all primary skin tumors. Herein, we report a case of malignant mixed tumor which recurred in the right thumb 20 years after the reported initial diagnosis of a benign mixed tumor at this site. Histologically, the lesion consisted of highly atypical and infiltrative cells in cords and ductal structures, with an adjacent focus of residual benign mixed tumor present. Perineural invasion of multiple dermal and subcutaneous nerves was also seen. Immunohistochemical staining was strongly and diffusely positive for CK5/6 and p63, with patchy positive S100 and CK7 staining. Wide excision was performed, with no evidence of recurrence or metastasis 5 years later.

Evaluation and management of the patient with multiple syringomas: A systematic review of the literature.

Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma ("tadpole") shaped tail comprised of dilated, cystic eccrine ducts. Clinically, syringomas typically present in adolescent females predominantly in the periorbital region. They may present as solitary or multiple lesions, and more rare sites of involvement include the genitals, palms, scalp, and the chest. Over the past 50 years, there have been >800 reported cases of syringoma either alone or in conjunction with a systemic syndrome, most commonly Down syndrome. The primary aim of this systematic review is to discuss the clinical features and associations of syringomas with a focus on the patient with multiple syringomas. Its secondary aims are to explore pathophysiology with a focus on multiple syringomas and provide comprehensive data on both traditional and novel treatments. Importantly, multiple syringomas present across a broad clinical spectrum. Though noted in many textbooks to be related to tumor syndromes, the association of syringomas with inherited tumor syndromes is only rarely reported in the literature. Despite multiple reported cases of syringoma, the pathophysiology remains poorly understood and treatment continues to pose a significant challenge.

Carbon dioxide laser combined with botulinum toxin A for patients with periorbital syringomas.

BACKGROUND: Although various destructive methods have been described for treating syringomas, they are often associated with significant scarring and recurrence. In 2007, multiple-drilling method using carbon dioxide (CO2) laser was introduced as an alternative modality to gain good cosmetic results. OBJECTIVE: To retrospectively evaluate the effectiveness of CO2 laser combined with botulinum toxin A (BTXA) as treatment for syringomas. MATERIAL AND METHODS: Forty-eight patients with periorbital syringomas were treated with topical application of BTXA immediately after CO2 laser treatment. Forty-four patients were treated with CO2 laser only. RESULTS: Patients who were treated with CO2 laser combined with BTXA required significantly (p = 0.038) fewer treatment sessions compared with those treated with CO2 laser only. When the clinical improvements of the two treatment sessions were compared, the combined therapy (CO2 laser and BTXA) had significantly (p = 0.044) higher rate of results showing good (disappearance of 60-80% of lesion) or excellent (80-100%) than the CO2 laser only therapy (87.5% vs. 70.5%). CONCLUSIONS: CO2 laser combined with BTXA showed better effect than CO2 laser only.

Erbium YAG laser treatment of periorbital syringomas by using the multiple ovoid-shape ablation method.

INTRODUCTION: Syringomas are benign tumours that develop predominantly in the periorbital areas of women. As periorbital syringoma is adjacent to the appendages, Erbium YAG (Er:YAG) laser treatment should be an ideal tool for its precise ablation, although its use has not previously been reported. We retrospectively analysed our new ovoid-shape Er:YAG laser ablation method for the treatment of syringoma. MATERIALS AND METHODS: We developed an extirpation method in which multiple, 2- to 4-mm, egg-shaped ablation fields were created. This method was used to treat 49 patients, 35 of whom had predominantly accumulated syringomas, and 14 had disseminated syringomas. Treatment was repeated every 2 months. RESULTS: Our approach was successful in both disseminated- and accumulated-type syringoma as well as plaque-type syringoma, which is considered to be the most difficult to treat. After an average of 3.77 treatments, more than 75% of the syringoma in the treated area had disappeared in 43 of 49 patients. CONCLUSION: Our ovoid-shape ablation method gives good cosmetic results even in the most difficult type of syringoma.

Syringoma: A clinicopathological study of 244 cases.

BACKGROUND: Syringomas are benign tumours of the sweat glands, the most familiar clinical presentation of which is the presence of multiple lesions on the eyelids. The aim of our study was to determine the clinical and histological characteristics of a large series of patients and to examine anatomoclinical correlations. PATIENTS AND METHODS: This was a retrospective study conducted in all of the cases of syringoma analysed at the cutaneous histopathology laboratory in Strasbourg between 1970 and 2008. The clinical elements, patient history and diagnostic data were collated. All slides were re-read in order to determine the microscopic characteristics of the lesions. RESULTS: Two hundred and forty-four lesions were included. The sex ratio was 0.27 and the mean age was 42 years (8 to 85 years). Multiple syringomas were noted in 76% of cases, of which 29.2% were eruptive, and one case occurred in a setting of metastatic melanoma. The sites of predilection were the face (56.7%, of which 36.3% on the eyelids), the chest (18.1%) and the neck (17.5%) for the multiple forms. The lesions were in the form of papules (67%), either brown (34.2%) or flesh-coloured (19.8%). Pruritus was reported in 14 cases, including 4 at vulvar sites (out of a total of 8). A diagnosis of syringoma was made by the clinician in only 30.2% of the multiple forms, with mastocytosis being proposed in 7.1% of cases. The clear-cell forms (18 cases) presented no special clinical features. CONCLUSION: Syringomas are frequently multiple and are seen mainly in women. They are found predominantly on the face and trunk, and lesions are generally brown and pruritic, a little-known feature that accounts for the degree of diagnostic confusion with mastocytosis. The vulvar forms, which are often pruritic, are poorly known. The eruptive forms may include a hormonal component.

Treatment of periorbital syringoma by the pinhole method using a carbon dioxide laser in 29 Asian patients.

BACKGROUND: Pinhole method has been used to treat various types of scars and dermal tumors by making multiple small holes in target tissues of the deep dermis using an ablative 10,600-nm carbon dioxide (CO2) laser. OBJECTIVES: We prospectively investigated the efficacy and safety of using a CO2 laser to treat periorbital syringomas via the pinhole method. METHODS: A total of 29 patients with periorbital syringomas were treated with two sessions of CO2 laser treatment using the pinhole method at two-month intervals. Laser fluences were delivered under the following settings: pulse duration of 200 µs, frequency of 50 Hz, on time of 0.04, and an off time of 0.01. RESULTS: Among the 29 patients, 13 patients (44.8%) presented with small discrete papular syringomas, 10 (34.5%) had plaque-type lesions, and six (20.7%) had mixed lesions. Evaluation of the clinical results at 2 months after the second treatment session revealed marked clinical improvement (51-75%) in 10 of the 29 patients (34.5%), moderate clinical improvement (26-50%) in eight (27.6%), near-total improvement (≥ 75%) in seven (24.1%), and minimal improvement (0-25%) in four patients (13.8%). CONCLUSIONS: Our observations indicated that application of the pinhole method using a CO2 laser exerts positive therapeutic effects in Asian patients with periorbital syringomas.

[Cutaneous chondroid syringoma]. / Syringome chondroïde cutané.

INTRODUCTION: Chondroid syringoma (CS) is a rare cutaneous tumor characterized by mixte epithelial and mesenchymal component. The confident histological diagnosis can be obtained by immuno-histochemistry study. Here we present 10 new cases with their clinico-hystological characteristics. METHODS: The 10 cases were observed between January 2000 and august 2013, in Fort-de-France and Louis-Mourier universitary hospitals. For all the cases a controlled histological study was performed by a dermatopathologist expert and immuno-histochemistry was added. Clinical and immuno-histological data were analyzed. RESULTS: The lesions were almost localized on the face (3/10) and the extremities (3/10). The size was about 1.2 to 5.2cm. Every case was treated by surgery, no malignant case was diagnosed. Histologically, all the 10 cases presented as a well-limited dermic tumor with a mixte epithelial and mesenchymal component. The stroma was myxo-chondroid, and the epithelial component consisted in epithelial cavities lined by one or two cell layers with eccrine (4/10) or apocrine (5/10) features. Immuno-chemistry study reveals positivity for EMA, ACE and CK7 for the internal cells, and positivity for S100 protein and vimentin of the extern cell layer. DISCUSSION: Chondroid syringoma is characterized by a mixte epithelial with eccrine and apocrine cells and a myxo-chondroid stroma. Our study has some clinical and histological particularities (lesions on the extremities, epidermic connecting…). The main differentials diagnoses are the other annexial tumors. The treatment is surgical. CONCLUSION: The histological diagnosis of CS is quite easy, but in case of doubt, immuno-chemistry will help, showing a double mesenchymal and epithelial differentiation.