Thermal Boundary Resistance Extraction of GaN-on-Diamond Substrate from Transmission Line Method Pattern Using Micro-Raman Spectroscopy and Thermal Simulation.

Heat dissipation properties are very important in AlGaN/GaN RF high electron mobility transistor (HEMT) devices operating at high frequency and high power. Therefore, in order to extract the thermal conductivity of the substrate and device, which are essential for the analysis of the heat dissipation characteristics, various methods of extraction were attempted. And this experiments were conducted in parallel with micro-raman measurement and thermal simulation. As a result, it was possible to extract the thermal conductivity of each GaN-on-diamond epi layer by matching the thermal simulation data and the shift of the micro-raman peak according to various operating states and temperatures of the transmission line method (TLM) pattern. In particular, we tried to extract the thermal boundary resistance (TBR) of the interface layer (SiNx) for adhesion between GaN and diamond, which greatly affects the thermal conductivity of the device, and successfully extracted the following thermal conductivity value of KTBR = 3.162·(T/300)-0.8 (W/mK) from GaN and diamond interface layer.

Heat dissipative mechanical damping properties of EPDM rubber composites including hybrid fillers of aluminium nitride and boron nitride.

As highly integrated electronic devices and automotive parts are becoming used in high-power and load-bearing systems, thermal conductivity and mechanical damping properties have become critical factors. In this study, we applied two different fillers of aluminium nitride (AlN) and boron nitride (BN), having polygonal and platelet shapes, respectively, into ethylene-propylene-diene monomer (EPDM) rubber to ensure improved thermo-mechanical properties of EPDM composites. These two different shapes are considered advantageous in providing effective pathways of phonon transfer as well as facilitating sliding movement of packed particles. When the volume ratio of AlN : BN was 1 : 1, the thermal conductivity of the hybrid-filler system (EPDM/AlN/BN) increased in comparison to that of the single-filler system (EPDM/AlN) of 3.03 to 4.76 W m-1 K-1. The coefficient of thermal expansion (CTE) and thermal distortion parameter (TDP) substantially decreased from 59.3 ppm °C-1 and 17.5 m K-1 of EPDM/AlN, to 39.7 ppm °C-1 and 8.4 m K-1 of EPDM/AlN/BN, representing reductions of 33 and 52%, respectively. Moreover, the damping coefficient of EPDM/AlN/BN was greatly increased to 0.5 of at 50 °C, compared to 0.03 of neat EPDM. These excellent performances likely stem from the effective packing of AlN/BN hybrid fillers, which could induce facile energy transfer and effective energy dissipation by the sliding movement of the adjacent hybrid fillers in the EPDM matrix.

Molecular Characterization of Neuroendocrine-like Bladder Cancer.

PURPOSE: Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5% to 15% of muscle-invasive bladder cancer (MIBC) have transcriptomic patterns consistent with NE bladder cancer in the absence of NE histology. The clinical implications of this NE-like subtype have not been explored in depth. EXPERIMENTAL DESIGN: Transcriptome-wide expression profiles were generated for MIBC collected from 7 institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; n = 175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort (n = 225). A random forest model was finalized and applied to 5 validation cohorts (n = 1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes. RESULTS: In the training cohort (PTC), hierarchical clustering using an 84-gene panel showed a cluster of 8 patients (4.6%) with highly heterogeneous expression of NE markers in the absence of basal or luminal marker expression. NE-like tumors were identified in 1% to 6.6% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression-free survival (65% NE-like vs. 82% overall; P = 0.046) and, after adjusting for clinical and pathologic factors, had a 6.4-fold increased risk of all-cause mortality (P = 0.001). IHC confirmed the neuronal character of these tumors. CONCLUSIONS: A single-patient classifier was developed that identifies patients with histologic urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC, which may require different treatment.

SOX10 immunohistochemistry in sweat ductal/glandular neoplasms.

BACKGROUND: SOX10 is a newer Schwannian and melanocytic marker that has generated great interest for its relative sensitivity and specificity in the diagnosis of neural crest-derived tumors. Previous studies with SOX10 have shown positive immunohistochemical expression in cutaneous eccrine glands and negative expression in eccrine ducts, apocrine glands and hair follicles. Thus, we hypothesized that some sweat gland tumors of presumed eccrine origin would be positive for SOX10, whereas apocrine-derived sweat gland tumors would not. METHODS: A mouse monoclonal anti-SOX10 (clone BC34: Biocare Medical; Concord, California) immunohistochemical antibody was performed on various sweat gland tumors and basal cell carcinoma. RESULTS: SOX10 showed positivity in spiradenomas (13/13), cylindromas (9/10), hidradenoma papilliferum (10/10), syringocystadenoma papilliferum (8/10), apocrine adenomas (8/10), and negativity in poromas (0/12), syringomas (0/10), and basal cell carcinomas (0/13). There was mixed staining of hidradenomas (6/15). CONCLUSIONS: SOX10 immunohistochemistry may be of utility in distinguishing some of the varying adnexal tumors from each other, and from basal cell carcinoma (BCC), but given the staining of both apocrine and eccrine tumors, does not seem to provide information as to their origins as either eccrine or apocrine tumors.

Molecular Analysis of Low Grade Prostate Cancer Using a Genomic Classifier of Metastatic Potential.

PURPOSE: We determined how frequently histological Gleason 3 + 3 = 6 tumors have the molecular characteristics of disease with metastatic potential. MATERIALS AND METHODS: We analyzed prostatectomy tissue from 337 patients with Gleason 3 + 3 disease. All tissue was re-reviewed in blinded fashion by genitourinary pathologists using 2005 ISUP (International Society of Urological Pathology) Gleason grading criteria. A previously validated Decipher® metastasis signature was calculated in each case based on a locked model. To compare patient characteristics across pathological Gleason score categories we used the Fisher exact test or the ANOVA F test. The distribution of Decipher scores among different clinicopathological groups was compared with the Wilcoxon rank sum test. The association of Decipher score with adverse pathology features was examined using logistic regression models. The significance level of all statistical tests was 0.05. RESULTS: Of men with Gleason 3 + 3 = 6 disease only 269 (80%) had a low Decipher score with intermediate and high scores in 43 (13%) and 25 (7%), respectively. Decipher scores were significantly higher among pathological Gleason 3 + 3 = 6 specimens from cases with adverse pathological features such as extraprostatic extension, seminal vesicle involvement or positive margins (p <0.001). The median Decipher score in patients with margin negative pT2 disease was 0.23 (IQR 0.09-0.42) compared to 0.30 (IQR 0.17-0.42) in patients with pT3 disease or positive margins (p = 0.005). CONCLUSIONS: Using a robust and validated prognostic signature we found that a small but not insignificant proportion of histological Gleason 6 tumors harbored molecular characteristics of aggressive cancer. Molecular profiling of such tumors at diagnosis may better select patients for active surveillance at diagnosis and trigger appropriate intervention during followup.

Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy.

BACKGROUND: Despite salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) after radical prostatectomy (RP), some patients still progress to metastases. Identifying these men would allow them to undergo systemic therapy including testing novel therapies to reduce metastases risk. OBJECTIVE: To test whether the genomic classifier (GC) predicts development of metastatic disease. DESIGN, SETTING, AND PARTICIPANTS: Retrospective multi-center and multi-ethnic cohort study from two academic centers and one Veterans Affairs Medical Center in the United States involving 170 men receiving SRT for recurrent PCa post-RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time from SRT to development of metastatic disease tested using Cox regression, survival c-index, and decision curve analysis. Performance of GC was compared to the Cancer of the Prostate Risk Assessment Score and Briganti risk models based on these metrics. RESULTS AND LIMITATIONS: With a median 5.7 yr follow-up after SRT, 20 patients (12%) developed metastases. On multivariable analysis, for each 0.1 unit increase in GC (scaled from 0 to 1), the hazard ratio for metastasis was 1.58 (95% confidence interval 1.16-2.17; p=0.002). Adjusting for androgen deprivation therapy did not materially change the results. The c-index for GC was 0.85 (95% confidence interval 0.73-0.88) versus 0.63-0.65 for published clinico-pathologic risk models. The 5-yr cumulative incidence of metastasis post-SRT in patients with low, intermediate, and high GC scores was 2.7%, 8.4%, and 33.1%, respectively (p<0.001). CONCLUSIONS: While validation in larger, prospectively collected cohorts is required, these data suggest GC is a strong predictor of metastases among men receiving SRT for recurrent PCa post-RP, accurately identifying men who are excellent candidates for systemic therapy due to their very high-risk of metastases. PATIENT SUMMARY: Genomic classifier and two clinico-pathologic risk models were evaluated on their ability to predict metastases among men receiving salvage radiation therapy for recurrent prostate cancer. Genomic classifier was able to identify candidates for further therapies due to their very high-risk of metastases.

Validation of a Genomic Classifier for Predicting Post-Prostatectomy Recurrence in a Community Based Health Care Setting.

PURPOSE: We determined the value of Decipher®, a genomic classifier, to predict prostate cancer outcomes among patients after prostatectomy in a community health care setting. MATERIALS AND METHODS: We examined the experience of 224 men treated with radical prostatectomy from 1997 to 2009 at Kaiser Permanente Northwest, a large prepaid health plan in Portland, Oregon. Study subjects had aggressive prostate cancer with at least 1 of several criteria such as preoperative prostate specific antigen 20 ng/ml or greater, pathological Gleason score 8 or greater, stage pT3 disease or positive surgical margins at prostatectomy. The primary end point was clinical recurrence or metastasis after surgery evaluated using a time dependent c-index. Secondary end points were biochemical recurrence and salvage treatment failure. We compared the performance of Decipher alone to the widely used CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical) score, and assessed the independent contributions of Decipher, CAPRA-S and their combination for the prediction of recurrence and treatment failure. RESULTS: Of the 224 patients treated 12 experienced clinical recurrence, 68 had biochemical recurrence and 34 experienced salvage treatment failure. At 10 years after prostatectomy the recurrence rate was 2.6% among patients with low Decipher scores but 13.6% among those with high Decipher scores (p=0.02). When CAPRA-S and Decipher scores were considered together, the discrimination accuracy of the ROC curve was increased by 0.11 compared to the CAPRA-S score alone (combined c-index 0.84 at 10 years after radical prostatectomy) for clinical recurrence. CONCLUSIONS: Decipher improves our ability to predict clinical recurrence in prostate cancer and adds precision to conventional pathological prognostic measures.

A Rare Case of a Pilar Cyst With Ductal Differentiation.

Pilar cysts are common squamous-lined cysts that typically occur on the scalp. They are believed to arise from the isthmus of anagen hairs or from the sac surrounding catagen and telogen hairs. The authors describe a rare case of a pilar cyst with prominent ductal differentiation, presumably of eccrine derivation. Sweat duct differentiation has been described in a myriad of cutaneous neoplasms and rarely within epidermoid cysts. The authors could only find one other case in the literature describing a pilar cyst with sebaceous and apocrine differentiation. The clinicopathologic findings are described here.

Characterization of primary cutaneous CD8+/CD30+ lymphoproliferative disorders.

CD30 primary cutaneous lymphoproliferative diseases include both lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (PCALCL). The neoplastic cell of most primary CD30 lymphoproliferative disorders is CD4 positive. The terminology LyP "type D" has been used to describe a growing number of cases of LyP with a predominantly CD8 infiltrate. PCALCL with a CD8 phenotype has also been described, which presents a particularly difficult diagnostic and management challenge, given the difficulty in distinguishing it histologically from other cytotoxic lymphomas such as primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma and CD8 gamma/delta and natural killer/T-cell lymphoma. We report 7 additional cases of these rare cutaneous CD8/CD30 lymphoproliferative disorders. We also present a unique case of CD8/CD30 LyP with histologic similarities to LyP type B. In all 7 of our cases of CD8 LyP and CD8 anaplastic large cell lymphoma, we found focal to diffuse MUM-1 positivity. We propose that MUM-1 may represent an adjunctive marker for CD8 lymphoproliferative disease. Finally, we review the current literature on cases of CD8 LyP and PCALCL. For the 106 cases examined, we found similar clinical and histologic features to those reported for traditional CD4CD30 LyP and PCALCL.

Keratoacanthoma and squamous cell carcinoma are distinct from a molecular perspective.

Keratoacanthoma is a controversial entity. Some consider keratoacanthoma as a variant of squamous cell carcinoma, whereas others see it as a distinct self-resolving squamoproliferative lesion. Our objective is to examine the relationship of keratoacanthoma with squamous cell carcinoma and normal skin by using DNA microarrays. DNA microarray studies were performed on formalin-fixed and paraffin-embedded blocks from ten cases of actinic keratoacanthoma utilizing the U133plus2.0 array. These results were compared with our previously developed microarray database of ten squamous cell carcinoma and ten normal skin samples. Keratoacanthoma demonstrated 1449 differentially expressed genes in comparison with squamous cell carcinoma (>5-fold change: P<0.01) with 908 genes upregulated and 541 genes downregulated. Keratoacanthoma showed 2435 differentially expressed genes in comparison with normal skin (>5-fold change: P<0.01) with 1085 genes upregulated and 1350 genes downregulated. The most upregulated genes, comparing keratoacanthoma with normal skin included MALAT1, S100A8, CDR1, TPM4, and CALM1. The most downregulated genes included SCGB2A2, DCD, THRSP, ADIPOQ, adiponectin, and ADH1B. The molecular biological pathway analysis comparing keratoacanthoma with normal skin showed that cellular development, cellular growth and proliferation, cell death/apoptosis, and cell cycle pathways are prominently involved in the pathogenesis of keratoacanthoma. The most enriched canonical pathways were clathrin-mediated endocytosis signaling, molecular mechanisms of cancer and integrin signaling. The distinctive gene expression profile of keratoacanthoma reveals that it is molecularly distinct from squamous cell carcinoma. The molecular pathways and genes differentially expressed in comparing keratoacanthoma with normal skin suggest that keratoacanthoma is a neoplasm that can regress due to upregulation of the cell death/apoptosis pathway.

A newly developed mouse monoclonal SOX10 antibody is a highly sensitive and specific marker for malignant melanoma, including spindle cell and desmoplastic melanomas.

CONTEXT: Recent immunohistochemical studies have demonstrated Sry-related HMG-Box gene 10 (SOX10) expression in malignant melanomas, malignant peripheral nerve sheath tumors, a subset of breast carcinomas, and gliomas. SOX10 has shown important clinical utility in its ability to detect desmoplastic and spindle cell melanomas. To date, most publications have employed a research use-only goat polyclonal SOX10 antibody for immunohistochemical staining. OBJECTIVE: To describe the development of a new mouse monoclonal SOX10 antibody (BC34) and evaluate its immunohistochemical staining profile in a wide range of normal and neoplastic tissues, with an emphasis on melanoma. DESIGN: SOX10 antibody was optimized for staining using a polymer detection system and visualization with diaminobenzidine. RESULTS: In normal tissues, SOX10 was expressed in skin melanocytes and eccrine cells, breast myoepithelial and lobular epithelial cells, salivary gland myoepithelial cells, peripheral nerve Schwann cells, and central nervous system glial cells. SOX10 was expressed in 238 of 257 melanomas (92.6%), including 50 of 51 of both spindle cell and desmoplastic melanomas (98%). SOX10 was expressed in 100% of nevi (20 of 20) and schwannomas (28 of 28). In other neoplasms, SOX10 was expressed in 18 of 109 invasive ductal breast carcinomas (16.5%). All other carcinomas were negative for SOX10. SOX10 was identified in 25 of 52 central nervous system neoplasms, primarily in astrocytomas (22 of 41; 53.7%), and in 4 of 99 various sarcomas examined (4.0%). CONCLUSIONS: The newly developed mouse monoclonal SOX10 antibody BC34 is highly sensitive and specific for malignant melanoma, including desmoplastic and spindle cell variants, and appears highly suitable for clinical use.

Prescribing Patterns of Pain Medication in Hospitalized Elderly Patients with Non-Cancer Pain

OBJECTIVE: Pain is very common in the elderly, so there is a high prevalence of analgesic use among this population. The purpose of this study was to assess patterns of analgesic use and evaluate factors associated with analgesic use in elderly patients. METHOD: The subjects of this study were patients over 65 years old hospitalized in a teaching hospital located in Chuncheon-si, Korea between January 1, 2014 and March 31, 2014. Data collection regarding analgesic prescriptions and baseline characteristics was conducted using computerized hospital database by medical information team. Logistic regression analysis was used to identify factors related to analgesic use. RESULTS: A total of 2,394 patients were finally included. Among these patients, 700 (29.2%) took analgesics; 521 (74.4%) out of these 700 patients were received opioid analgesics and 179 (25.6%) were received only non-opioid analgesics. The most frequently prescribed opioid analgesic was pethidine (45.7%), and the most frequently prescribed non-opioid analgesic was acetaminophen (44.1%). Fracture was associated with increased odds of opioid analgesic prescriptions (OR = 2.766, 95% CI = 2.019-3.790, p < 0.001) and any analgesic prescriptions (OR = 2.394, 95% CI = 1.766-3.244, p < 0.001). Stroke or cerebral infarction was associated with decreased odds of opioid analgesic prescriptions (OR = 0.636, 95% CI = 0.471-0.858, p = 0.003). CONCLUSION: A significant proportion of hospitalized elderly patients use analgesics. Health care professionals should consider factors associated with analgesic use in this population to improve pain management.

Intralymphatic cutaneous anaplastic large cell lymphoma/lymphomatoid papulosis: expanding the spectrum of CD30-positive lymphoproliferative disorders.

Intravascular large B-cell lymphomas and EBV NK/T-cell lymphomas commonly follow an aggressive clinical course. We recently reported an entirely intravascular anaplastic large cell lymphoma (ALCL) in the skin with a surprisingly indolent clinical course; interestingly, this lymphoma involved the lymphatic rather than the blood vasculature. We hypothesized that intravascular skin-limited ALCL is distinct from aggressive systemic intravascular lymphomas in its intralymphatic localization and clinical course. We now describe 18 cases of cutaneous intravascular large cell lymphoproliferations from 4 institutions. All 12 intravascular large T-cell lesions were intralymphatic; the majority (9) were CD30 T-cell lymphoproliferative disorders (TLPDs), 5 further classified as intravascular ALK ALCL. One ALK ALCL and 2 benign microscopic intravascular T-cell proliferations were also intralymphatic. A single case of otherwise typical cutaneous follicle center lymphoma contained intralymphatic centroblasts. The clinical and pathologic characteristics of the CD30 TLPDs were similar to those of their extravascular counterparts, including extralymphatic dermal involvement in a subset, DUSP22-IRF4 translocations in half of tested ALK ALCLs, and associated mycosis fungoides in 1; most were skin-limited at baseline and remained so at relapse. All 5 cases of intravascular large B-cell lymphoma involved the blood vasculature and behaved in a clinically aggressive manner; the ALK ALCL, although intralymphatic, was systemic and clinically aggressive. We propose that cutaneous ALK ALCL and related CD30 ALK TLPDs involving the lymphatics are part of an expanding spectrum of CD30 TLPDs. The identification of intralymphatic as distinct from blood vascular localization may provide critical prognostic and therapeutic information.

Differentiating cutaneous squamous cell carcinoma and pseudoepitheliomatous hyperplasia by multiplex qRT-PCR.

Squamous cell carcinoma is the second most common cutaneous malignancy. The diagnosis can occasionally be difficult as there are many lesions that are mimics, clinically and on pathologic examination. One of the most challenging lesions to differentiate from squamous cell carcinoma is pseudoepitheliomatous hyperplasia, a reactive proliferation of the epidermis that can be encountered secondary to a variety of inflammatory and neoplastic conditions. Utilizing the data set from our previously performed DNA microarray studies on formalin-fixed and paraffin-embedded tissue, we found that the genes C15orf48 and KRT9 had a distinct and robust gene expression pattern in distinguishing squamous cell carcinoma from pseudoepitheliomatous hyperplasia. C15orf48 had higher expression than KRT9 in squamous cell carcinoma, but lower expression than KRT9 in pseudoepitheliomatous hyperplasia. We developed and blindly validated a multiplex TaqMan PCR assay that utilizes these two highly discriminatory genes, which can be performed on material extracted from formalin-fixed and paraffin-embedded tissue. The TaqMan assay was able to differentiate squamous cell carcinoma from pseudoepitheliomatous hyperplasia in 54 of 58 cases (93%). Squamous cell carcinoma was accurately identified in 27 of 28 cases (96%); pseudoepitheliomatous hyperplasia in 27 of 30 cases (90%). This multiplex TaqMan PCR assay may be used as a helpful ancillary molecular diagnostic test to accurately distinguish squamous cell carcinoma from pseudoepitheliomatous hyperplasia in challenging cases.

Molecularly enriched pathways and differentially expressed genes distinguishing cutaneous squamous cell carcinoma from pseudoepitheliomatous hyperplasia.

INTRODUCTION: Cutaneous squamous cell carcinoma (SCC) is one of the most commonly diagnosed nonmelanoma skin cancers. Occasionally, the diagnosis can be challenging as there are many simulating preneoplastic and reactive squamous lesions. One of the most difficult lesions to differentiate from SCC is pseudoepitheliomatous hyperplasia (PEH). The objective of our study is to differentiate cutaneous SCC from PEH using gene expression microarrays and examine the enriched molecular pathways and genes. DESIGN: DNA microarray studies were performed on formalin-fixed and paraffin-embedded blocks of the skin: 10 cases of SCCs and 10 cases of PEHs using the U133 plus 2.0 array. RESULTS: A total of 703 differentially expressed genes were identified between SCCs and PEHs (>2-fold change, P<0.05) including multiple upregulated S100 calcium-binding proteins and downregulated homeobox genes. Functional analysis of these genes suggests that oxidative phosphorylation, mitochondrial dysfunction and the polyamine regulation pathways are involved in the pathogenesis of SCC. CONCLUSIONS: The distinctive gene expression profile of SCC and PEH offers the ability to use DNA microarrays to distinguish between them by an objective molecular measure. The molecular pathways and differentially expressed genes provide an insight into the pathogenesis of SCCs and may serve as future targets for therapeutic intervention.

Leukemia cutis in association with cutaneous epidermal malignancies.

BACKGROUND: Epidermal malignancies developing in association with hematolymphoid malignancies are exceptional. Only one prior case of myeloid leukemia cutis with a cutaneous epidermal malignancy has been reported. METHODS: We report two cases; one occurred in association with squamous cell carcinoma (SCC) and another with basal cell carcinoma (BCC). RESULTS: Both patients were 83-year-old males without established histories of systemic hematopoietic disorders; one presented with an erythematous papule on the right upper back and the other with a nodule on the left wrist. One biopsy revealed nodular BCC with an associated perivascular myeloid leukemic infiltrate showing immunohistochemical positivity for CD43 and CD45. The other biopsy showed SCC associated with a leukemic infiltrate in sheets with myeloid blasts, eosinophilic myelocytes and maturing myeloid precursors. The myeloid cells showed immunohistochemical expression of CD43, CD68, CD33, CD117 and myeloperoxidase. Both patients had myeloblasts on peripheral blood smear. One patient declined further treatment and died of disease 5 weeks after the initial biopsy. The other patient underwent chemotherapy and is alive after 6 months. CONCLUSION: Although most inflammatory infiltrates associated with cutaneous epidermal malignancies are reactive, careful examination is necessary to exclude systemic hematopoietic disease, especially in elderly patients.

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin.

Actinic keratosis is widely believed to be a neoplastic lesion and a precursor to invasive squamous cell carcinoma. However, there has been some debate as to whether actinic keratosis is in fact actually squamous cell carcinoma and should be treated as such. As the clinical management and prognosis of patients is widely held to be different for each of these lesions, our goal was to identify unique gene signatures using DNA microarrays to discriminate among normal skin, actinic keratosis, and squamous cell carcinoma, and examine the molecular pathways of carcinogenesis involved in the progression from normal skin to squamous cell carcinoma. Formalin-fixed and paraffin-embedded blocks of skin: five normal skins (pooled), six actinic keratoses, and six squamous cell carcinomas were retrieved. The RNA was extracted and amplified. The labeled targets were hybridized to the Affymetrix human U133plus2.0 array and the acquisition and initial quantification of array images were performed using the GCOS (Affymetrix). The subsequent data analyses were performed using DNA-Chip Analyzer and Partek Genomic Suite 6.4. Significant differential gene expression (>2 fold change, P<0.05) was seen with 382 differentially expressed genes between squamous cell carcinoma and normal skin, 423 differentially expressed genes between actinic keratosis and normal skin, and 9 differentially expressed genes between actinic keratosis and squamous cell carcinoma. The differentially expressed genes offer the possibility of using DNA microarrays as a molecular diagnostic tool to distinguish between normal skin, actinic keratosis, and squamous cell carcinoma. In addition, the differentially expressed genes and their molecular pathways could be potentially used as prognostic markers or targets for future therapeutic innovations.

Melanocytic matricoma with melanocytic atypia: report of a unique case and review of the literature.

Melanocytic matricoma is a rare cutaneous neoplasm of presumed anagen hair follicle origin with approximately 10 reported cases in the literature. Melanocytic matricomas are clinically and histopathologically distinct cutaneous nodular proliferations of matrical and supramatrical cells admixed with dendritic melanocytes, which typically occur in the sun-exposed areas of elderly patients. We report a new case with additional histopathologic features not previously described. An 82-year-old white man presented with an exophytic papule of the ear clinically suspicious for basal cell carcinoma. Histopathologic examination demonstrated a polypoid neoplasm consisting of an admixture of matrical and shadow cells with numerous interspersed dendritic and epithelioid melanocytes arranged singly and in large expansile nests. An unusual feature in this case included prominent melanocytic proliferation with associated nuclear atypia and increased mitotic activity. Although atypical and malignant melanocytic colonization has been reported in basal cell carcinomas and squamoproliferative lesions, to our knowledge, it has not been previously described in melanocytic matricomas. The biologic significance of atypical melanocytic proliferations within melanocytic matricomas is uncertain and requires further study of additional cases and long-term follow-up.