Beatriz Llombart

Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers.

Aims:  To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers.

Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial tumor characterized by high rates of local recurrence and low risk of metastasis. DFSP occurs most commonly on the trunk and proximal extremities, affects all races, and often develops between the second and fifth decade of life. The tumor grows slowly, typically over years. Histologically, several variants of DFSP have been described and should be well characterized to avoid misdiagnosis with other tumors. These include pigmented (Bednar tumor), myxoid, myoid, granular cell, sclerotic, atrophic DFSP, giant cell fibroblastoma, and DFSP with fibrosarcomatous areas. Of all these variants, only the DFSP with fibrosarcomatous areas is high grade, with a higher rate of local recurrence and distant metastasis. DFSP is genetically characterized by the t(17;22)(q22;q13), resulting in the fusion of alpha chain type 1 of collagen gene and platelet-derived growth factor beta gene. This translocation is present in 90% of DFSP and represents a very useful tool in the differential diagnosis of DFSP with other tumors with similar histology. The standard treatment is wide local excision with at least a 2-cm margin. However, local recurrence after apparently adequate surgical excision is well recognized. Mohs micrographic surgery would be the treatment of choice with a better cure rate and maximal conservation of tissue. When surgery is insufficient, clinical evidence has suggested that imatinib mesylate is a safe and effective treatment in DFSP, especially in cases of local advanced or metastatic disease. This article presents an overview of the state of the art in the clinicopathological management of this disease.

Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1‐PDGFB ) study with therapeutic implications

Aims: To analyse the presence of collagen type I alpha 1–platelet‐derived growth factor beta (COL1A1–PDGFB) transcripts in 20 cases of dermatofibrosarcoma protuberans (DFSP) and to assess the relationship between COL1A1 breakpoints and clinical and histopathological variables.

Comparative study between cold air analgesia and supraorbital and supratrochlear nerve block for the management of pain during photodynamic therapy for actinic keratoses of the frontotemporal zone

Background  Photodynamic therapy (PDT) is an effective treatment for actinic keratoses, Bowen’s disease and basal cell carcinoma. The main drawback of PDT is pain during application.

A randomized pilot comparative study of topical methyl aminolevulinate photodynamic therapy versus imiquimod 5% versus sequential application of both therapies in immunocompetent patients with actinic keratosis: Clinical and histologic outcomes

BACKGROUND Photodynamic therapy (PDT) and imiquimod are the treatments of choice for actinic keratosis (AK). As they have different mechanisms of action, it seems reasonable to assume that applying both treatments sequentially would be efficacious. OBJECTIVES We sought to determine which of these therapeutic modalities provides a better clinical and histologic response in patients with AK and whether sequential use of both was more efficacious than each separately. METHODS Patients were randomly assigned to one treatment group: group 1, PDT only; group 2, imiquimod only; or group 3, sequential use of PDT and imiquimod. The primary outcome measure was complete clinical response. Partial clinical response was defined as a reduction of more than 75% in the initial number of lesions. A complete clinicopathologic response was defined as lack of evidence of AK in the biopsy specimen. RESULTS In all, 105 patients completed the study (group 1, 40 patients; group 2, 33 patients; group 3, 32 patients). Sequential application of PDT and imiquimod was more efficacious in all the outcome measures. More patients were satisfied with PDT than with the other two modalities (P = .003). No significant differences were observed among the 3 modalities and tolerance to treatment. LIMITATIONS Only one cycle of imiquimod was administered. The follow-up period was brief. CONCLUSIONS Sequential application of PDT and imiquimod provides a significantly better clinical and histologic response in the treatment of AK than PDT or imiquimod monotherapy. It also produces less intense local reactions and better tolerance and satisfaction than imiquimod monotherapy.

Molecular diagnosis of dermatofibrosarcoma protuberans: a comparison between reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization methodologies.

Dermatofibrosarcoma protuberans (DFSP) is characterized by the presence of the t(17;22)(q22;q13) that leads to the fusion of the COL1A1 and PDGFB genes. This translocation can be detected by multiplex reverse transcriptase‐polymerase chain reaction (RT‐PCR) or fluorescence in situ hybridization (FISH) techniques. We have evaluated the usefulness of a dual color dual fusion FISH probe strategy for COL1A1/PDGFB detection in a series of 103 archival DFSPs and compared the obtained results with RT‐PCR analyses. FISH and RT‐PCR were carried out on paraffin embedded tissue samples. Regarding the RT‐PCR approach, all COL1A1 exons and exon 2 of PDGFB were evaluated. Sensitivity, specificity, positive and negative predictive values were assessed considering the histological diagnosis as the gold standard. We also analyzed the relationship between the genetic findings and the clinicopathological variables of the tumors. The COL1A1/PDGFB translocation was detected in 93% of DFSP. Both techniques showed a similar specificity (100%), but FISH was more sensitive than RT‐PCR (90% vs. 72%). Regarding, clinicopathological features, a higher percentage of positive cells detected by FISH was significantly associated with the fibrosarcomatous DFSP variant (P < 0.001). Interestingly, all CD34 negative DFSP (n = 5) were positive for COL1A1/PDGFB translocation by both techniques. In conclusion, the majority of DFSP harbor the COL1A1/PDGFB translocation and FISH technique should be recommended as a routine diagnostic tool, especially in cases showing unusual histopathological subtypes and/or immunohistochemical features.

Cutaneous epithelioid angiomatous nodule: a case series and proposed classification.

Cutaneous epithelioid angiomatous nodule is a peculiar and recently recognized vascular proliferation. Clinically, these lesions affect different areas of the body and histologically are characterized by a well-circumscribed, mainly unilobular, solid proliferation of endothelial cells with prominent epithelioid features. The cytoplasm is abundant and eosinophilic, and many of the neoplastic cells contain prominent vacuoles. Inflammatory infiltrates are variable. All the cases reported thus far have followed a benign course. We report 10 additional cases of this curious entity, including 2 which presented in an eruptive fashion and 5 that were located on the head and neck. We also discuss the histological differential diagnoses with other epithelioid proliferations and propose categorization within the spectrum of epithelioid hemangioma.

Correlation Between Preoperative Magnetic Resonance Imaging and Surgical Margins with Modified Mohs for Dermatofibrosarcoma Protuberans

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is characterized by asymmetrical and poorly defined growth. Magnetic resonance imaging (MRI) has been proposed for the delimitation of this tumor. OBJECTIVES To study the utility of MRI in evaluating the depth of infiltration in DFSP and to compare the efficiency of clinical palpation with that of MRI in delimiting the invasiveness of DFSP. METHODS Observational, prospective study of DFSP cases. The MRI scans for all cases were compared with the exact histological infiltration plane obtained using modified Mohs micrographic surgery (MMS). RESULTS Forty‐three DFSPs were included: 22 primary, nine recurrent, and 12 extirpated with positive margins. Sensitivity for detecting deep invasion was 58% on examination using palpation and 67% using MRI. CONCLUSIONS We present the largest series of DFSP cases studied using MRI published to date. In primary cases, MRI has greater sensitivity than palpation for detecting depth of infiltration (67% vs 58%). MRI seems to be useful in primary DFSP in locations other than the head, neck, and upper part of the thorax. MRI is not useful for confirming tumor persistence in extirpated DFSP with positive margins or for studying lateral extension in primary DFSP. The authors have indicated no significant interest with commercial supporters.

A randomized comparative study of tolerance and satisfaction in the treatment of actinic keratosis of the face and scalp between 5% imiquimod cream and photodynamic therapy with methyl aminolaevulinate

Background  Photodynamic therapy (PDT) and imiquimod are two excellent treatments for actinic keratosis but are often not well tolerated by patients.

Fluorescence in situ hybridization for the differential diagnosis between Spitz naevus and spitzoid melanoma

Requena C, Rubio L, Traves V, Sanmartín O, Nagore E, Llombart B, Serra C, Fernández‐Serra A, Botella R & Guillén C 
(2012) Histopathology 61, 899–909