Therapeutic outcomes and survival analysis of Extramammary Paget's disease: A multicentre retrospective study of 249 patients.

BACKGROUND: Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited. OBJECTIVES: To assess the DSS and outcomes of surgical and nonsurgical therapeutic modalities in a large cohort of EMPD patients. METHODS: Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals. RESULTS: Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively. LIMITATIONS: Retrospective design. CONCLUSIONS: EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.

Treatment of extramammary Paget disease with imiquimod in a real-life setting: a multicentre retrospective analysis in Spain.

BACKGROUND: Topical imiquimod has been shown to be an effective treatment for extramammary Paget disease (EMPD), although available evidence supporting its use is based on case reports and small series of patients. OBJECTIVES: To investigate the therapeutic outcomes and analyse potential clinicopathological factors associated with the imiquimod response in a large cohort of patients with EMPD. METHODS: Retrospective chart review of 125 patients with EMPD treated with imiquimod at 20 Spanish tertiary-care hospitals. RESULTS: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) treatments achieving a complete response (CR), 41 (30.6%) a partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥ 6 cm; P = 0.04) and EMPD affecting > 1 anatomical site (P = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤ 4 vs. > 4 times per week; P = 0.112). Among patients who achieved CR, 30 of 69 (43%) treatments resulted in local recurrences during a mean follow-up period of 36 months, with an estimated 3- and 5-year recurrence-free survival of 55.7% and 36.4%, respectively. CONCLUSIONS: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favourable therapeutic response could be expected in larger lesions and those affecting > 1 anatomical site. Based on our results, a three to four times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for patients with EMPD.

[[Translated article]]Avelumab to treat Merkel cell carcinoma: real-life experience in a dedicated oncology center.

The arrival of immunotherapy has revolutioned the management of patients with metastatic Merkel cell carcinoma (MCC). We conducted an observational, retrospective study of 14 cases treated with avelumab. The response rate was 57%: complete response was reached in 29% of patients, and partial responses in 29%. The drug proved effective in 83% (5/6) of the patients with a single metastatic site. However, the disease progressed in 75% (3/4) of the patients with bone metastases. PD1-L expression, MCC polyomavirus (MCPyV) positivity, and an impaired neutrophil-to-lypmhocyte ratio (NLR) could not be associated with responses to the therapy. Avelumab is an effective and safe drug for the management of advanced MCC, and its effectiveness appears to be impacted by the number and location of metastases.

Combined Merkel cell carcinoma and cutaneous squamous cell carcinoma with lymph node metastases: Report of two cases.

Merkel cell carcinoma (MCC) is an infrequent, aggressive cutaneous neoplasm, that typically affects the photodamaged skin of elderly individuals, and immunosuppressed patients. Because a subset of MCC is closely related to UV radiation, MCC can develop concurrently with other tumors, most commonly, as a combined tumor with squamous cell carcinoma (SCC). These combined tumors appear to represent a distinct disease process from pure MCC, as they are mostly Merkel cell polyomavirus (MCPyV) negative, and show a more aggressive behavior. We present two additional cases of combined MCC and SCC with nodal metastases, one of which was MCPyV positive. Two different subtypes of MCC have been proposed based on their origin: a true neuroendocrine carcinoma, that is MCPyV positive and has a dermal origin, and a UV-related SCC with neuroendocrine differentiation. This theory could explain why MCC can develop concurrently with SCC, and why these combined cases are generally MCPyV negative. However, it fails to explain the minority of combined MCC and SCC tumors that are MCPyV positive. Because both our patients had a history of chronic UV exposure, we hypothesize that UV radiation probably played a major role in the pathogenesis of these tumors, while MCPyV integration probably acted as an additional trigger.

Trichoepithelioma on the Finger: A Rare Location and Dermoscopic-Histopathologic Correlation.

ABSTRACT: Trichoepithelioma is a benign adnexal neoplasm of follicular germinative cells, with bulbs, papillae, and sheaths of perifollicular connective tissue as signs of follicular differentiation. Accordingly, trichoepithelioma may arise in any hair-bearing location, mostly on the face. That is why trichoepithelioma cannot appear in glabrous skin, and, although the dorsum of the hands and feet are a hair-bearing area, acral location is exceptional. We report the first case of trichoepithelioma localized in the finger of a 79-year-old man. It was a brown-pink, firm, 7-mm diameter, solid papule on the dorsal aspect of his left index finger. The lesion was completely asymptomatic, and he remembered to have it for many years. We describe this case highlighting its rare anatomical location and correlate its dermoscopic features with the histopathological appearance.

Determination of Margins for Tumor Clearance in Dermatofibrosarcoma Protuberans: A Single-Center Study of 222 Cases Treated With Modified Mohs Surgery.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an invasive skin tumor traditionally associated with very high recurrence rates when treated with conventional surgery (CS). OBJECTIVE: To calculate the minimum margin that would have been required to achieve complete tumor clearance with hypothetical CS. To analyze DFSP characteristics and Mohs micrographic surgery (MMS) effectiveness in treatment of this tumor. MATERIALS AND METHODS: Minimum margin was calculated by measuring the largest distance from the visible edge of the tumor to the edge of the surgical defect. Tumor variables (age, sex, size, time since onset, and location) were correlated with surgical variables (number of stages and minimum margin). RESULTS: We studied 222 cases of DFSP treated with MMS. A mean of 1.47 MMS stages and a mean minimum margin of 1.23 cm were required to achieve tumor clearance. Tumors on the head and neck required significantly more stages and a significantly wider margin. Tumor size was positively correlated with time to diagnosis, age, and number of MMS stages. CONCLUSION: Tumors located on the head and neck have greater subclinical extension. Tumor size was also a predictor of surgical difficulty, but time to diagnosis was not.

Cutaneous Ossifying Amyloidoma.

ABSTRACT: Amyloidoma, otherwise known as tumoral amyloidosis, is a localized deposition of amyloid (AL-type or AA type) without systemic amyloidosis. It is the rarest form of tissue amyloid deposition, and up to 7% of amyloidomas develop systemic amyloidosis.Cutaneous AL-type amyloidoma is considered by many authors as an unusual variant of primary cutaneous marginal zone lymphoma. Although cutaneous amyloidoma can form calcifications, ossification is extremely unusual, with only 1 case previously published to date.We report the case of a 75-year-old woman with voluminous and strikingly ossifying AL-type amyloidoma in the left pretibial skin. Her medical history included excision of hepatic hydatidic cysts 25 years prior and diffuse large B-cell lymphoma of the left parotid gland 8 years prior treated with chemotherapy and radiotherapy with complete response. After the diagnosis of amyloidoma, an extension study with cervical, chest, abdominal, and pelvic TC was performed, with no additional lesions found. Serum and protein electrophoresis revealed elevations in kappa light chain and IgA immunoglobulin levels but did not reveal monoclonal bands. In situ hybridization for immunoglobulin light chains showed monotypic kappa expression in plasma cells infiltrating the amyloidoma.Extensive ossification in amyloidomas can make diagnosis difficult; therefore, we describe an interesting case of this histopathologically peculiar amyloidoma.

Usefulness of ultrasound in dermatofibrosarcoma protuberans and correlation with histopathological findings: A series of 30 cases.

BACKGROUND: Small series of ultrasound findings in dermatofibrosarcoma protuberans (DFSP) have been published, but the usefulness of this technique as a preoperative planning tool for tumor resection has not been studied. MATERIALS AND METHODS: We retrospectively reviewed patients with DFSP at our hospital that underwent ultrasound examination. Depth of invasion was evaluated by ultrasound and histopathology. Accuracy of ultrasound for assessing depth of tumor invasion was estimated. RESULTS: Thirty histopathologically confirmed DFSPs were studied. Classic finger-like projections were observed in 73.3% of cases. A posterior hyperechoic area extending deep into the subcutaneous tissue correlated with the honeycomb DFSP pattern and was observed in 53.3% of patients. Concordance between ultrasound and histopathologic depth measurements was excellent. Lateral tumor extension and Doppler activity were not evaluated in our series. CONCLUSION: Ultrasound showed excellent prediction of depth of invasion. Further studies are required to define the usefulness of ultrasound for determining lateral tumor extension.

Predictive Value of Sentinel Lymph Node Biopsy in Cutaneous Squamous Cell Carcinoma Based on the AJCC-8 and Brigham and Women's Hospital Staging Criteria.

BACKGROUND: Recommendations on when to perform sentinel lymph node (SLN) biopsy in cutaneous squamous cell carcinoma (cSCC) are lacking despite the tumor's clear predilection for lymphatic spread. OBJECTIVE: To analyze the frequency of SLN metastasis in published series of cSCC in the context of the eighth edition of the American joint Committee on Cancer (AJCC-8) and the Brigham and Women's Hospital (BWH) staging criteria. METHODS: Systematic review of studies of patients with cSCC who underwent SLN biopsy that described biopsy results. RESULTS: In total, 153 patients with 24 positive SLN biopsies (15.7%) were included. Based on the AJCC-8 criteria positivity rates in the T2 and T3 categories were 8.3% (1/12 patients) and 25% (8/32), respectively. Using the BWH system there were, 2/33 in category T2a (6.5%), and 5/17 in category T2b (29.8%). On applying the same criteria to tumors of the trunk and extremities the results were similar. CONCLUSION: It would seem reasonable to recommend SLN biopsy for patients with AJCC-8 Stage T3+ disease or BWH Stage T2b/T3 disease. Both the AJCC-8 and the BWH systems would appear to be useful for staging cSCC of the trunk and extremities.

Multiple facial plaque variant of trichoblastoma.

BACKGROUND: The plaque variant of trichoblastoma has been described as a solitary tumor with diffuse infiltration of the lower dermis and hypodermis, with poorly defined borders. Herein, we report a new variant of multiple centrofacial trichoblastoma. OBJECT: To describe clinical and pathological features of a new multiple kind of plaque variant of centrofacial trichoblastoma. METHODS: Case series of patients with a multiple-plaque variant of centrofacial trichoblastoma treated in our department between 2005 and 2017. We identified eight patients with the centrofacial plaque variant of trichoblastoma treated in our department from 2005 to 2017. RESULTS: The final study sample comprised 13 trichoblastomas from four patients. All patients also developed at least one basal cell carcinoma. Mohs surgery was the method of treatment in the majority of the cases of trichoblastoma and in all the cases of basal cell carcinoma. We needed between 2 and 6 stages to obtain free margins in our cases of facial plaque trichoblastomas treated by Mohs surgery. CONCLUSION: To the best of our knowledge, a multiple-plaque variant of trichoblastoma has not been described in the literature. We suggest a genetic origin of this variant of trichoblastoma and describe its remarkable infiltrative nature, with poorly defined surgical margins.

Immunohistochemical and Fluorescence In Situ Hybridization Analysis of MYC in a Series of 17 Cutaneous Angiosarcomas: A Single-Center Study.

Cutaneous angiosarcoma (AS) is an uncommon, aggressive sarcoma whose incidence is rising because of the increasing use of radiation therapy, especially in breast cancer. The few studies on the relevance of prognostic factors, such as MYC status in cutaneous AS, have reported inconclusive findings, with some authors reporting MYC amplification only in postirradiation and lymphedema-associated AS and others reporting evidence of MYC amplification in idiopathic AS. We analyzed 17 cases of cutaneous AS (6 idiopathic AS, 10 postirradiation AS, and 1 lymphedema-associated AS) treated at our institute between 2000 and 2015. Follow-up data were available in all cases. We compared the presence/absence of MYC amplification by fluorescence in situ hybridization (FISH) and immunohistochemical (IHC) MYC overexpression in the different AS subtypes. We also investigated potential associations between MYC amplification and prognosis. MYC amplification was observed by FISH in 6 of 14 informative cases. The positive cases were all secondary AS (5 postirradiation AS and 1 lymphedema-associated AS). IHC detected MYC overexpression in 8 of 15 informative cases (7 secondary AS and 1 idiopathic AS). In conclusion, MYC amplification and MYC overexpression were detected almost exclusively in secondary AS. No associations were found between MYC amplification/overexpression and prognosis. We found MYC amplification or overexpression in a similar proportion of the patients who died and who were still alive at the end of the study. In the group of 9 patients who died, MYC was detected by FISH in 4 cases and by IHC in 5. The corresponding figures in the group of 6 patients still alive were 2 by FISH and 3 by IHC.

Subcutaneous dermatofibrosarcoma protuberans, a rare subtype with predilection for the head: A retrospective series of 18 cases.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) typically affects the dermis and subcutaneous tissue. The subcutaneous variant is rare. OBJECTIVE: We sought to characterize the subcutaneous DFSP (SC-DFSP) variant and compare it with cutaneous DFSP (C-DFSP). METHODS: This work was a retrospective study of DFSP treated in our institution. RESULTS: Of 124 cases of DFSP, 18 were SC-DFSP (14.5%). Except for the deep location, the pathologic and genetic features were indistinguishable from the C-DFSP variant. Histologically, of 18 SC-DFSP cases, 13 were classic DFSP, 3 fibrosarcomatous DFSP (FS-DFSP), 1 Bednar tumor, and 1 giant-cell fibroblastoma. All tumors expressed CD34 and the COL1A1-PDGFB fusion transcripts. In our series, higher proportions of SC-DFSP tumors (61%) than C-DFSP tumors (8.5%) were located on the head (P < .001). Of the 20 DFSP tumors on the head (16.1%), 11 were SC-DFSP and 9 were C-DFSP. In addition, half the SC-DFSP tumors affected muscle or periosteum, compared with a quarter of the C-DFSP tumors (P = .009). SC-DFSP needed a higher number of Mohs stages than did C-DFSP (P = .009). Median follow-up time was 63 months, and 2 FS-DFSP tumors recurred (1 SC-DFSP, 1 C-DFSP). LIMITATIONS: Limitations include the retrospective aspect of the study. CONCLUSIONS: Most DFSP tumors involving the head were subcutaneous and required more complex surgery. Dermatologists should be aware of this atypical presentation, especially in lesions involving the head.

Desmoplastic melanoma may mimic a cutaneous peripheral nerve sheath tumor: Report of 3 challenging cases.

Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100-positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major nerve, pre-existing neural benign tumor or the existence of stigmata suggestive of neurofibromatosis raised consideration of a DM. Careful attention should be paid to the presence of a firm dermal nodule and atypical scar lesions especially in sun-exposed areas (mainly head and neck region) in elderly patients associated with S100-positive spindle cell proliferation, solar elastosis and adjacent atypical melanocytic proliferation. In such cases, the possibility of a DM should be excluded with caution, especially if the tumor reveals a paucicellular morphology resembling various non-melanocytic neoplasms including malignant or benign peripheral sheath nerve tumors.

Skin involvement as the first manifestation of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a newly described clinical and pathologic entity that typically presents as seroma in the fibrous scar around the implant. Less frequently, it presents as a solid peri-implant mass, and there have been no reports to date of cutaneous lesions as the presenting manifestation. We report the case of a 56-year-old woman with a history of bilateral breast reconstruction following breast cancer of the right breast who consulted with several papules on the right breast suggestive of metastasis. Histopathology showed a proliferation of large epithelioid lymphocytes with highly pleomorphic cells and nuclei. The neoplastic cells were CD15 and CD30 positive and ALK-1 negative. The epithelial markers were all negative except for epithelial membrane antigen (EMA), which was weakly positive. Molecular analysis showed monoclonal T-cell receptor γ gene rearrangement, confirming a diagnosis of breast implant-associated ALCL. The non-specific morphology of the skin lesions, the epithelioid nature of the neoplastic cells and the expression of EMA can lead to an erroneous diagnosis of skin metastases from a poorly differentiated adenocarcinoma of the breast. We recommend immunohistochemical staining for CD30 and ALK-1 for patients with breast implants who develop anaplastic lesions.

Antimalarial Drugs for the Treatment of Oral Erosive Lichen Planus.

BACKGROUND: Treatment of oral erosive lichen planus is considered a therapeutic challenge. Various systemic and topical agents aimed at controlling the symptoms, rather than curing the lesions, have been used with varying results. OBJECTIVE: To evaluate the response to treatment with antimalarial drugs in patients with oral erosive lichen planus. METHODS: Eight patients diagnosed with oral erosive lichen planus were treated with antimalarial agents. The first clinical evaluation was made after a month of treatment and then every 2-3 months. Baseline ophthalmologic examinations were performed, and laboratory values were monitored before and during treatment. RESULTS: All studied patients who had previously been resistant to other treatments responded favorably. Pain relief and reduced erythema and erosions were observed after of a mean of 2.4 months. CONCLUSION: Antimalarials may be useful for the treatment of oral erosive lichen planus. They are easily administered and affordable, with few adverse effects.

Biphasic dermatofibrosarcoma protuberans with a labyrinthine plexiform high-grade fibrosarcomatous transformation.

Several variants of dermatofibrosarcoma protuberans, a low-grade superficial sarcoma, are well recognized. The most prognostically important is the fibrosarcomatous variant. We report a case of biphasic dermatofibrosarcoma protuberans in which the high-grade component exhibited a previously undescribed plexiform pattern. A clinicopathological study complemented with immunohistochemical, ultrastructural, reverse transcription polymerase chain reaction and fluorescence in situ hybridization analyses of this unique case. Histopathologically, a conventional low-grade dermatofibrosarcoma protuberans was admixed with intratumoral high-grade areas showing a striking labyrinthine plexiform pattern characterized by a higher cellularity of larger and slightly atypical tumor cells. CD34 expression was present in both components, while Ki-67 immunostaining was significantly higher in the plexiform high-grade areas. Focal epithelial membrane antigen and claudin-1 immunostaining was present at the interphase between high- and low-grade areas. COL1A1-PDGFB fusion transcripts, with breakpoints at exon 25 of COL1A1 and exon 2 of PDGFB, were present in both components, being more numerous, as the extra copies of both genes, in the high-grade areas. A previously undescribed histopathologic pattern of high-grade sarcomatous transformation of dermatofibrosarcoma protuberans is reported: a biphasic tumor with a labyrinthine plexiform high-grade component.

Awareness, Attitude, and Adherence to Preventive Measures in Patients at High Risk of Melanoma. A Cross-Sectional Study on 185 Patients.

Melanoma is potentially curable if diagnosed at its earliest stages and treated properly. The best approaches for reducing deaths due to melanoma are primary and secondary prevention. The objective of this study is to evaluate patient awareness of the risk factors for developing melanoma and attitudes toward its prevention. Also, this study aims to assess observance of recommended preventive measures and to identify possible factors associated with a low adoption of these measures. This cross-sectional study based on an online questionnaire included 185 consecutively enrolled subjects at risk of developing melanoma monitored in a pigmented lesion unit in Valencia (Spain). Level of knowledge, attitude, and observance of preventive measures were evaluated. Statistical analysis was carried out using contingency tables, chi-squared test, and Spearman correlation. Out of those who reported practicing skin self-examination, only 24.1 % performed it in the optimal way. A better attitude was observed in low-risk patients (r = -0.28, p < 0.01). Being female (p < 0.01), aged 18-35 (p = 0.02), fair-haired (p = 0.02), having skin phototype I-II (p < 0.01), and a suitable attitude (p = 0.05) and knowledge (p < 0.01) were related to a better use of sunscreens and avoidance of sun exposure. Knowledge was inversely associated with age (p = 0.01). Despite the high level of knowledge and positive attitude, inadequate practice of compliance with recommended primary and secondary preventive measures was observed in our risk population.