Mireia Yébenes

Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas

Please cite this paper as: Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas. Experimental Dermatology 2010; 19: 151–153.

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.

Epithelial to mesenchymal transition markers are associated with an increased metastatic risk in primary cutaneous squamous cell carcinomas but are attenuated in lymph node metastases

BACKGROUND Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epithelial to mesenchymal transition (EMT) is a process involving loss of intercellular adhesion, acquisition of a mesenchymal phenotype and enhanced migratory potential; epithelial markers, such as E-cadherin, are down-regulated and mesenchymal proteins (Vimentin), increased. OBJECTIVE To investigate the expression of EMT markers in metastatic SCC (MSCC) and their corresponding metastases, and to correlate them with clinico-pathological factors associated with an increased risk of metastasis. METHODS We performed a retrospective study that included 146 cSCC samples (51 primary non-metastatic, 56 primary metastatic, 39 lymphatic metastases). Immunohistochemistry for E-cadherin, Vimentin, Snail, beta-catenin, Twist, Zeb1 and Podoplanin was performed. RESULTS Loss of membranous E-cadherin was observed in 77% cSCCs, with no differences between MSCC and non-MSCC. Among the transcriptional factors controlling EMT, no significant Snail1 expression was detected. Twist, Zeb1, Vimentin, beta-catenin and Podoplanin were significantly overexpressed in MSCCs. Twist ectopic expression in SCC13 cells induced Zeb1, Vimentin and Podoplanin expression and E-cadherin delocalization. These changes resulted in a scattered migration pattern in vitro. Expression of EMT markers was decreased in the metastases when compared with the corresponding primary tumors. CONCLUSION These results suggest that a partial EMT, characterized by the expression of Twist but without a total E-cadherin depletion, is involved in the acquisition of invasive traits by cSCC, but the process is downregulated in lymph node metastases.

Multiple genetic copy number alterations in oral squamous cell carcinoma: study of MYC, TP53, CCDN1, EGFR and ERBB2 status in primary and metastatic tumours

Background  Oncogenesis in the oral cavity is believed to result from genetic alterations that cause a stepwise transformation of the mucosa to invasive carcinoma. In oral squamous cell carcinoma (OSCC) multiple cytogenetic abnormalities have been reported, but their practical significance remains uncertain.

Identification of t(17;22)(q22;q13) (COL1A1/PDGFB) in dermatofibrosarcoma protuberans by fluorescence in situ hybridization in paraffin-embedded tissue microarrays

Dermatofibrosarcoma protuberans is genetically characterized by the translocation t(17;22)(q22;q13) resulting in the PDGFB/COL1A1 fusion gene. Fluorescence in situ hybridization with specific probes enables a rapid detection of this gene. In this study, the presence of the translocation t(17;22)(q22;q13) by fluorescence in situ hybridization in paraffin-embedded tissue microarrays was analyzed. Two tissue microarrays including 40 cases of dermatofibrosarcoma protuberans and 20 dermatofibromas were evaluated. Fluorescence in situ hybridization analyses were performed using a dual-color dual-fusion noncommercial probe. Clinical and histopathologic features were examined, and the association with fluorescence in situ hybridization results was assessed. A total of 29 samples of dermatofibrosarcoma protuberans and 16 of dermatofibromas were successfully evaluated. Twenty-five (86%) dermatofibrosarcoma protuberans samples were positive for the translocation, which was absent in all samples of dermatofibromas. Two of the negative dermatofibrosarcoma protuberans showed unusual, hypercellular areas with marked cytologic atypia, whereas 1 case exhibited overlap features with dermatofibroma. Tumors with fibrosarcomatous areas seemed to have a higher percentage of positive cells and the number of copies of the COL1A1/PDFGB gene. In conclusion, the COL1A1/PDGFB fusion gene was present in most of the dermatofibrosarcoma protuberans tissue samples. The detection of the translocation may be an additional diagnostic tool in cases of dermatofibrosarcoma protuberans showing nonconclusive histologic features.

D2-40 immunohistochemical overexpression in cutaneous squamous cell carcinomas: A marker of metastatic risk

BACKGROUND Approximately 4% of cutaneous squamous cell carcinomas (cSCCs) develop lymphatic metastases. The value of lymphatic endothelial markers to enhance the detection of lymphatic tumor invasion in cSCC has not been assessed previously. OBJECTIVE We sought to evaluate the use of the antibody D2-40, a podoplanin immunohistochemical marker, to identify tumor lymph vessel invasion in cSCC and to assess its expression in tumor cells. METHODS This was a retrospective case-control study. A series of 101 cSCC, including 51 cases that developed lymphatic metastatic spread (metastasizing cSCC [MSCC]) and 50 cases that resolved definitely after surgical excision (non-MSCC) were included in the study. Lymph vessel invasion using D2-40 was evaluated on all primary biopsy specimens. The percentage of tumor cells showing D2-40 positivity and intensity scoring were recorded. All the immunohistochemical findings were correlated with the clinicopathological features. RESULTS Lymph vessel invasion was observed in 8% of non-MSCCs and in 25.5% of MSCCs (P = .031). D2-40 expression was significantly increased, both in intensity (odds ratio 4.42 for intensity ++/+++) and in area (odds ratio 2.29 for area >10%), in MSCC when compared with non-MSCC. Interestingly, almost half (49%) of the MSCC had moderate to intense D2-40 positivity compared with 16% of non-MSCC. D2-40 immunohistochemical expression was increased in tumors with an infiltrative pattern of extension. In the multivariate analysis, histologically poorly differentiated tumors, recurrent lesions, and cSCC showing D2-40 overexpression (in intensity) were significantly associated with lymphatic metastases development (odds ratios 15.67, 14.72, and 6.07, respectively). LIMITATIONS This was a retrospective study. CONCLUSION The expression of podoplanin associates with high metastatic risk in cSCC.

Cranial Fasciitis in an 8‐Year‐Old Boy: Clinical and Histopathologic Features

Abstract:  Cranial fasciitis is an uncommon benign disorder characterized by a fibroblast‐like cell proliferation, observed almost exclusively in children. Clinically, it manifests as a rapidly growing, solitary nodule in the head or neck area. Underlying bone involvement (cranial cortical erosion) is frequently detected. Histopathologic analysis allows differentiation between cranial fasciitis and fibrohistiocytic or even sarcomatous lesions observed in children. Cranial fasciitis is considered to be a reactive, non‐neoplastic disorder and is usually cured by a simple excision. An increased awareness of the clinical and histopathologic characteristics of this entity seems important to establish the diagnosis, to adopt an adequate, conservative treatment and to avoid unnecessarily aggressive procedures.

Depot leuprorelin acetate-induced granulomas manifested as persistent suppurative nodules

) is a synthetic agonist analogue of gonadotrophin-releasing hormone (Gn-RH or luteinizing hormone-releasing hormone), administered as intramuscular or subcutaneous injections, and indicated for the treatment of advanced prostate cancer. In the last decade, sustained release parenteral depot formulations have been developed, by entrapping the hydrophilic leuprorelin in biodegradable highly lipophi-lic synthetic polymer microspheres. Depending on the type of polymer being used, the peptide drug is released from these depot formulations at different constant rates. Polylactic and glycolic acids (PLGA) are used for a one-month depot injections, and polylactic acid (PLA) for depot injections longer than 2 months. Cutaneous adverse events to leuprorelin acetate are rare, but several cases of local reactions at the injection sites have been reported in urology or paediatric journals (1–5). These reactions have been described as erythematous ma-cules, infiltrated plaques, subcutaneous nodules and sterile abscesses. A possible role of either leuprorelin acetate itself or lipophilic synthetic polymer used in depot injections has been postulated as responsible for such reactions (6). A 78-year-old man was referred to our department for evaluation of a persistent inflammatory suppurative subcutaneous nodule on his right arm. Past medical history disclosed a familial protein C deficiency (treated with acenocoumarol and without any vascular complication) and advanced prostate cancer diagnosed in 1988. During the last months, the patient was receiving injections with 3-month depot formulation of leuprorelin acetate. Since he was receiving treatment with oral anticoagulants, the injections were administered subcutaneously instead of intra-muscularly (the recommended route). Four months before consultation, the patient noticed a painful erythematous subcutaneous papule-nodule developing at the injection site of the third dose of leuprorelin acetate. The lesion had appeared a few days after the injection, and had enlarged progressively, developing a central ulcer. Treatment with oral antibiotics (amoxicillin/clavulanic acid) was prescribed without any clinical improvement. Physical examination disclosed an apparently healthy man presenting a fistulated subcutaneous nodule, 3 cm in diameter, on the lateral aspect of his right arm. It was a painful lesion that drained a dense serous material. No fever, malaise, regional enlarged lymph nodes or hepatosplenomegaly were noted. Several bacteriological, mycobacteriological and fungal cultures from swabs obtained from the exudate yielded negative results. Treatment with oral tetracycline and clarithromycin, as well as topical cures with mupirocin, was prescribed and the lesion resolved in 2 months. During the following months, the patient developed two additional similar lesions on the left buttock (Fig. 1) and on …

Localized retiform purpura after accidental intra-arterial injection of polidocanol.

Sir, Non-inflammatory retiform (net-like or livedoid) purpura (NIRP) is a clinical pattern produced by small vessel occlusion in dermis. Several disorders such as coagulation abnormalities, cold-related gelling, microorganism vessel invasion or embolization leading to microvascular occlusion may share in common a clinical picture of localized or generalized NIRP (1). NIRP lesions are usually sharply demarcated and sometimes erythematous plaques, from a few millimetres to many centimetres in size, which subsequently become necrotic. The livedoid appearance can be diffuse or localized at the margins of large necrotic purpuric lesions. Early lesions tend to have minimal or no erythema, whereas in more advanced lesions, necrosis takes place. We report here a case of localized NIRP after intra-arterial injection of polidocanol during treatment for lower limb varicosities.

Cutaneous Desmoid Tumor: Resolution of the Surgical Defect with a Dermal Regeneration Template and an Epidermal Autograft

Desmoid tumors (DTs) belong to the group of fibromatoses. They are slow-growing tumors that can be subdivided into fascial superficial fibromatoses and extra-abdominal fibromatoses. The most widely accepted classification of fibromatosis is that introduced by Enzinger and Weiss (Table 1). The first group comprises Dupuytren’s contracture (palmar fibromatosis), Ledderhose disease (plantar fibromatosis), Peyronie’s disease (penile fibromatosis), holoderma (knuckle pads), and deep muscle– aponeurotic fibromatosis. DT, also known as aggressive fibromatosis, has been described in abdominal and extra-abdominal locations. It can arise on the abdominal wall after pregnancy or after surgical manipulation. A form has been associated with Gardner’s syndrome and familial adenomatous polyposis. Its biological behavior is locally aggressive, with progressive growth and a high rate of recurrence after surgery. Local or distant metastases are exceptional. Primary cutaneous DT is exceedingly rare and has seldom been reported in the medical literature. Its clinical and histologic appearance can be similar to dermatofibrosarcoma protuberans and fibrosarcoma, and differential diagnosis from these tumors is mandatory to establish correct treatment and prognosis.