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Scott R Florell

Publications and source records attributed to Scott R Florell.

At least 19 recordsLinked to original sources
PubMed2007

Cost-effective dynamic telepathology in the Mohs surgery laboratory utilizing iChat AV videoconferencing software.

BACKGROUND: Dynamic telepathology is the real-time transmission of histologic images from one pathologist to another by means of telecommunications technology. OBJECTIVE: The objective was to determine whether dynamic telepathology can be accomplished accurately and inexpensively by use of readily available off-the-shelf consumer products and software. METHODS: We attached a standard, consumer-grade, digital video camera to a microscope in the Mohs surgery laboratory and then transmitted via the Internet real-time histologic video images and audio to a consultant dermatopathologist by means of iChat AV videoconferencing software (Apple Computer Inc., Cupertino, CA). In the first part of the study, 20 unknown formalin-fixed, paraffin-embedded slides from tumors typically seen in a Mohs practice were evaluated by the consultant dermatopathologist. In the second part of the study, the Mohs surgeon consulted the dermatopathologist on 20 Mohs frozen section slides in which the surgeon had a particular question (e.g., "Is this part of a pilosebaceous unit or is this basal cell carcinoma?"). RESULTS: The video images were adequate for pathologic interpretation. There was agreement between conventional light microscopy and dynamic telepathology diagnosis in 19 of 20 tumors. There was complete agreement for all 20 Mohs frozen section consultations. CONCLUSION: Dynamic telepathology can be accomplished accurately and inexpensively by use of readily available consumer products and software.

Cost-Benefit Analysis↗
PubMed2007

Human herpesvirus 8 and iron staining are useful in differentiating Kaposi sarcoma from interstitial granuloma annulare.

We studied 20 granuloma annulare (GA) cases (10 interstitial and 10 palisaded) and 19 Kaposi sarcoma (KS) cases (9 "early" and 10 typical). Tissue sections were stained for iron, Hale colloidal iron, human herpesvirus 8 (HHV-8), CD31, CD34, CD68, collagen IV, factor XIIIa, and MIB-1. Iron staining of dermal tissue associated with the lesion was confirmed in all KS cases and no GA cases. Immunohistochemical stains for HHV-8 were positive in all 9 cases of early KS and most cases (9/10) of typical KS. All 20 cases of GA were HHV-8-. CD31, CD34, CD68, factor XIIIa, and MIB-1 were also stained but were difficult to interpret and did not seem specific for GA or KS. Iron staining and immunohistochemical HHV-8 staining in combination were reliable markers for KS compared with interstitial GA. MIB-1 fractions of less than 5% favored a diagnosis of GA, whereas fractions greater than 10% favored a diagnosis of KS. This study provides novel data characterizing iron staining in KS and details the use of iron staining, HHV-8, and MIB-1 to distinguish KS from GA.

Granuloma Annulare↗
PubMed2006

Population-based prevalence of CDKN2A mutations in Utah melanoma families.

Cyclin-dependent kinase inhibitor 2A (CDKN2A or p16) is the major melanoma predisposition gene. In order to evaluate the candidacy for genetic testing of CDKN2A mutations among melanoma prone families, it is important to identify characteristics that predict a high likelihood of carrying a CDKN2A mutation. We primarily used a unique Utah genealogical resource to identify independent melanoma prone families whom we tested for mutations in CDKN2A, cyclin-dependent kinase 4, and alternate reading frame. We sampled 60 families which met the inclusion criteria of two or more affected first-degree relatives. We found four different pathogenic CDKN2A mutations in five families, mutations of uncertain significance in two families, and known polymorphisms in three families. One of the mutations of uncertain significance, 5' untranslated region -25C>T, has not been previously described. Among our population-based set of Utah families, the prevalence of CDKN2A mutations was 8.2% (4/49); the overall prevalence when physician-referred pedigrees were also considered was between 8.3% (5/60) and 10% (6/60). Having four or more first- or second-degree relatives with melanoma, or a family member with > or =3 primary melanomas, correlated strongly with carrying a CDKN2A mutation. We observed a significantly elevated rate of pancreatic cancer in one of four families with a deleterious CDKN2A mutation.

Base Sequence↗
PubMed2006

Lentigo maligna/lentigo maligna melanoma: current state of diagnosis and treatment.

BACKGROUND: Lentigo maligna (LM) is a subtype of melanoma in situ that typically develops on sun-damaged skin. Presentation may be quite subtle and delayed diagnosis is common. Clinical margins are often ill defined. Histologic evaluation can be difficult due to the widespread atypical melanocytes that are present in the background of long-standing sun damage. Recurrence following standard therapies is common. OBJECTIVE: To review the clinical features, histopathology, and treatment options for LM. Emphasis is placed on recent advances in the treatment of LM. METHODS AND MATERIALS: Literature review. RESULTS: The estimated lifetime risk of LM progressing to LM melanoma is 5%. Standard excision of LM with 5 mm margins is insufficient in 50% of cases. The recurrence rate with standard excision ranges from 8 to 20%. Mohs surgery and staged excision may offer better margin control and lower recurrence rates (4-5%). Estimates of recurrence rates following nonsurgical therapies such as cryosurgery, radiotherapy, electrodessication and curettage, laser surgery, and topical medications range from 20 to 100% at 5 years. CONCLUSIONS: Adequate treatment of LM requires a comprehensive knowledge of the diagnostic features, histopathology, and treatment options. Surgical modalities with meticulous evaluation of tissue margins appears to offer the lowest rates of disease recurrence.

Cryotherapy↗
PubMed2006

Usefulness (or lack thereof) of immunophenotyping in atypical cutaneous T-cell infiltrates.

Our purpose was to evaluate the interobserver concordance for the diagnoses of mycosis fungoides (MF), atypical dermatoses (AD), and benign dermatoses (BD) and the impact of T-cell immunophenotyping on the diagnoses MF, AD, and BD. Specimens of MF (n = 57), AD (n = 27), BD and normal skin (n = 54) were reviewed by 2 hematopathologists and 1 dermatopathologist to establish diagnostic interobserver concordance by routine morphologic examination. Immunophenotyping was performed to evaluate expression of CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and MIB-1. The interobserver concordance was fair to moderate compared with the original diagnosis. Partial deletion of CD2 alone was associated significantly with MF. Epidermal deletions of 2 or 3 T-cell antigens or 2 T-cell antigens not including CD7 were associated significantly with MF. An elevated CD4/CD8 ratio correlated with MF. Morphologic features were most diagnostic of MF. Immunophenotyping generally resulted in downgrading of the reaction pattern but was helpful in distinguishing MF from benign dermatoses.

Adult↗
PubMed2005

Population-based analysis of prognostic factors and survival in familial melanoma.

PURPOSE: Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma. PATIENTS AND METHODS: This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk. RESULTS: Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2). CONCLUSION: These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.

Adult↗
PubMed2005

Proliferation, apoptosis, and survivin expression in a spectrum of melanocytic nevi.

BACKGROUND: Apoptosis is important for maintenance of tissue homeostasis and often dysregulated in cutaneous neoplasms. The apoptosis inhibitor survivin is expressed in melanoma and non-melanoma skin cancers and benign keratinocytic lesions. Its expression has not been studied in melanocytic nevi. OBJECTIVE: We determined the expression pattern of survivin in benign melanocytic nevi in comparison to markers of proliferation and apoptosis. METHODS: Six cases of each of the following melanocytic nevi were retrieved from a dermatopathology archive: compound dysplastic nevus, intradermal nevus, compound nevus, neurotized intradermal nevus, and Spitz nevus. Survivin expression was evaluated by in situ hybridization. Apoptotic and proliferation indices were calculated by counting immunoreactive cells in terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling and proliferating cell nuclear antigen immunostained sections, respectively. RESULTS: All nevi, regardless of histologic type, expressed survivin. Compound melanocytic lesions expressed survivin in both epidermal and dermal compartments. The apoptotic rate was low for dysplastic, compound, and Spitz nevi, and apoptotic cells were not identified in any neurotized nevus. The proliferative index was highest for Spitz nevi, while all other nevi demonstrated rare positive cells. CONCLUSIONS: Survivin is consistently expressed in benign melanocytic lesions, while apoptotic cells are rarely identified, suggesting the dysregulation of apoptotic pathways with the accumulation of cells in these neoplasms.

Adolescent↗
PubMed2005

Clinical and pathological features of pachyonychia congenita.

Pachyonychia congenita (PC) is a rare genodermatosis affecting the nails, skin, oral mucosae, larynx, hair, and teeth. Pathogenic mutations in keratins K6a or K16 are associated with the PC-1 phenotype whereas K6b and K17 mutations are associated with the PC-2 phenotype. Analysis of clinical, pathological, and genetic data from the literature and two research registries reveal that >97% of PC cases exhibit fingernail and toenail thickening, and painful plantar keratoderma. Prospective evaluation of 57 PC patients from 41 families revealed variable clinical findings: hyperhidrosis (79%), oral leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma (60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%), coarse or twisted hair (26%), early primary tooth loss (14%), and presence of natal or prenatal teeth (2%). Stratification of these data by keratin mutation confirmed the increased incidence of cyst formation and natal teeth among PC-2 patients, although cysts were more commonly seen in PC-1 than previously reported (25%-33%). Previously unreported clinical features of PC include development of painful oral and nipple lesions during breastfeeding, copious production of waxy material in ears, and inability to walk without an ambulatory aid (50%). Possible pathogenic mechanisms are discussed with respect to the clinicopathologic and genetic correlations observed.

Darier Disease↗
PubMed2004

UVB-induced apoptosis drives clonal expansion during skin tumor development.

The mechanism by which a single mutant cell clonally expands is usually assumed to involve an additional mutation in a cell cycle regulatory gene. An alternative mechanism for driving clonal expansion is apoptosis, which might create vacant stem cell compartments that can be repopulated by mutant cells. This model predicts that in a mouse with reduced apoptotic capacity (i) more mutated cells will appear initially but (ii) these cells will expand into clones more slowly than in wild-type animals. To test this hypothesis for ultraviolet B (UVB)-induced skin carcinogenesis, we examined UVB-induced p53 mutant clones and tumors in a transgenic (Tg) mouse (K14-Survivin) with skin-specific expression of the apoptosis inhibitor Survivin. To limit the effects of Survivin on apoptosis, without affecting epidermal proliferation or differentiation, we used Survivin expression levels and UVB doses that resulted in a 2-fold reduction in keratinocyte apoptosis. After 5 weeks of chronic UVB irradiation, newly created p53 mutant keratinocyte clones (indicative of initial mutation frequency) were 1.4-fold more frequent in K14-Survivin mice (P = 4 x 10(-6)). As predicted, this effect was reversed for clones growing by clonal expansion, which were rarer in Tg skin by 1.7-fold (P = 0.047). At 10 weeks large expanding Tg clones were rarer by a magnitude approaching the apoptosis differential (approximately 2-fold, P = 4 x 10(-5)). Survivin expression also retarded clonal expansion at later stages of tumor development. By 20 weeks 95% of animals carried tumors (primarily papillomas), which were 1.6-fold rarer in apoptosis-defective Tg mice (P = 0.03). In contrast, the rate of tumors attaining large size (> or =3 mm, P = 0.048) and converting to carcinoma was increased approximately 2-fold in Tg mice. Thus, Survivin-regulated apoptosis appears to suppress two stages that involve new mutations, initiation and malignant conversion, yet drives clonal expansion of existing p53 mutant cells.

Animals↗
PubMed2004

Effects of trastuzumab on epidermal growth factor receptor-dependent and -independent human colon cancer cells.

Little information is available as to the potential role of HER-2 as a therapeutic target in colon cancers, which express much fewer HER-2 receptors than breast cancer cells. Treatment of certain human colon cancer cell lines with the HER-2 inhibitory antibody mAb 4D5 demonstrated a role for HER-2 in mediating proliferation, apoptosis and tumorigenicity. However, only the cell lines that were dependent on autocrine EGFR-mediated cell proliferation were susceptible to the antiproliferative and antitumorigenic effects of HER-2 inhibition. The relative levels of HER-2, EGFR, HER-3 and HER-4 were not predictive of responsiveness to mAb 4D5. Treatment with HER-2 antibodies caused a decrease in HER-2 protein levels in all of the colon cancer cell lines and also significantly decreased EGFR levels but only in the EGFR-dependent cell lines. Treatment with mAb 4D5 caused the rapid ubiquitination and ligand-dependent downregulation of the EGFR in an EGFR-dependent colon cancer cell line. Treatment of athymic mice engrafted with EGFR-dependent colon cancer cells with mAb 4D5 caused tumor regression and a decrease in EGFR tyrosine phosphorylation in the tumor cells. EGFR-independent colon cancer cell xenografts were resistant to mAb 4D5 therapy. Combined inhibition of HER-2 and EGFR caused large areas of necrosis in EGFR-dependent colon cancer xenografts, suggesting a benefit of combined HER-2 and EGFR inhibitor therapy. Predicting clinical responsiveness of human colon cancer cells to anti-HER-2 and anti-EGFR therapy may require demonstration of EGFR tyrosine kinase dependency of the cells.

Animals↗
PubMed2004

Proliferation, apoptosis, and survivin expression in keratinocytic neoplasms and hyperplasias.

The dysregulation of apoptosis occurs in many cutaneous disease states. Several apoptosis inhibitors have been shown elevated in neoplasms and in some inflammatory conditions, but their relation to proliferative and apoptotic states has not been defined. We examined the expression of the apoptosis inhibitor survivin in a panel of keratinocytic neoplasms and hyperproliferative skin lesions using both immunohistochemistry and a newly developed in situ hybridization technique. Proliferation and apoptotic indices were also assessed by immunohistochemical staining for proliferating cell nuclear antigen and TUNEL, respectively. We found the highest rate of proliferation in verrucae and psoriasis followed by actinic keratosis, squamous and basal cell carcinoma, lichen simplex chronicus, and seborrheic keratosis; all were significantly (P < 0.05) higher than normal skin. Apoptotic rate was increased in squamous (P = 0.05) and basal cell carcinoma (P = 0.03), but not significantly different from normal skin in the other lesions tested. Survivin expression was seen in most neoplasms and hyperproliferative lesions, but not normal skin. Survivin expression was often restricted to the upper third of the epidermis in psoriasis and lichen simplex chronicus, whereas all the other lesions stained diffusely. Survivin expression appears to be a consistent feature of keratinocytic neoplasms and hyperproliferative lesions and may contribute to the formation of epidermal hyperplasia seen in all of these disease states.

Antigens, Neoplasm↗
PubMed2004

Longitudinal assessment of the nevus phenotype in a melanoma kindred.

Phenotypic characteristics of members of a melanoma prone kindred with a V126D CDKN2A gene mutation were monitored over approximately 15 y. Thirty-eight previously studied subjects were recruited. Participants underwent a complete skin examination by the same dermatologist who examined them initially. The size and location of all nevi were recorded on a body map diagram. Total nevus number (TNN) and total nevus density (TND) were determined. CDKN2A sequencing verified 13 mutation carriers and 16 non-carriers. Nine participants were spouse controls without a history of melanoma and did not carry a CDKN2A mutation. Mutation carriers demonstrated a greater mean TNN and TND at initial and follow-up examinations compared with non-carriers and continued to develop nevi rather than show nevus regression seen in non-carriers and spouse controls. Non-carriers showed an intermediate nevus phenotype between mutation carriers and spouse controls. Four of the 13 mutation carriers and one non-carrier have developed invasive melanoma. Over a 15-y interval, TNN and TND were increased in mutation carriers compared with non-carriers and spouse controls. Continued accumulation of nevi in mutation carriers supports a nevogenic role for this CDKN2A mutation. An intermediate nevus phenotype in non-carrier family members suggests the presence of additional modifier genes.

Adolescent↗
PubMed2004

CD117, CK20, TTF-1, and DNA topoisomerase II-alpha antigen expression in small cell tumors.

BACKGROUND: Distinguishing merkel cell carcinoma (MCC), small cell lung carcinoma (SCLC) metastatic to the skin, and atypical basal cell carcinoma (BCC) can be problematic in some cases. Significant differences in the biology of these tumors necessitate that they need to be distinguished from one another. METHODS: We evaluated the immunophenotypic characteristics of 22 MCCs, nine SCLCs, and 19 BCCs using antibodies to cytokeratin 20 (CK20), thyroid transcription factor-1 (TTF-1), CD117, and DNA topoisomerase II-alpha (topo II). RESULTS: Nineteen of 22 MCCs stained with the antibody to CK20, none stained with anti-TTF-1, and 13 stained with anti-CD117. No SCLC stained with anti-CK20, all stained with anti-TTF-1, and eight stained with anti-CD117. No BCC stained with any of the three markers. The proliferative index (PI), determined by the expression of topo II, was similar for SLCLs (mean 58.5 +/- 9.0%) and MCCs (mean 45.2 +/- 12.4%) and was lowest in BCCs (mean 25.0 +/- 8.7%). CONCLUSIONS: CK20 and TTF-1 appear to be reliable in distinguishing MCC from SCLC. CD117 is expressed in both MCC and SCLC, limiting its diagnostic utility. CK20, TTF-1, and CD117 are not expressed in BCC. The high PI seen in MCCs suggests a role for topoisomerase II inhibitors in their treatment.

Antigens, Neoplasm↗