Keratoderma blennorrhagicum.
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Acitretin↗
Biomedical subjects
Scott R Florell
Publications and source records attributed to Scott R Florell.
Survivin expression in mouse skin prevents papilloma regression and promotes chemical-induced tumor progression.
Induction of cutaneous squamous cell carcinoma (SCC) in mice, by topical chemical [9,10-dimethylbenzanthracene (DMBA) and phorbol 12-myristate 13-acetate (PMA)] application, is a multistep process involving papilloma formation and progression to carcinoma. We have generated a transgenic (Tg) mouse [keratin-14 (K14)-survivin] with skin expression of survivin, an inhibitor of apoptosis expressed in most human skin cancers and premalignant lesions. K14-survivin mice were resistant to DMBA-induced keratinocyte apoptosis. To investigate the role of survivin and apoptosis in cutaneous carcinogenesis, mice were treated once topically with DMBA followed by twice weekly with PMA for 32 weeks. Surprisingly, tumor formation was less frequent (31% versus 43%) and significantly delayed (P = 0.01) in K14-survivin mice compared with non-Tg littermates. On the other hand, papilloma regression was not observed in Tg mice, whereas 20% of papillomas regressed in non-Tgs; one SCC was generated in Tg mice, whereas none were seen in non-Tgs. To increase tumor formation and SCC in particular, a second experiment was performed with mice on a p53+/- background. Again, DMBA/PMA-induced tumor formation was less (71% versus 89%) and significantly delayed (P = 0.02) in K14-survivin p53+/- animals compared with p53+/- non-Tgs. Papilloma regression was also not observed in Tg p53+/- mice, whereas 10% of papillomas regressed in p53+/- non-Tgs. The rate of papilloma progression to SCC was 21% in Tg p53+/- mice compared with 12% in p53+/- non-Tgs. Papillomas did not reveal significant differences in mitotic or apoptotic indices. Survivin expression was detected in all of the tumors. These results indicate that despite a paradoxical negative effect on tumor formation, survivin expression prevents papilloma regression and promotes conversion to SCC, consistent with its expression in most skin cancers and their precursors.
9,10-Dimethyl-1,2-benzanthracene↗
Histopathologic recognition of involved margins of lentigo maligna excised by staged excision: an interobserver comparison study.
OBJECTIVES: To assess interobserver and intraobserver concordance for identifying positive and negative margins in staged excisions of lentigo maligna and lentigo maligna melanoma and to determine if control biopsy specimens are useful to improve concordance. DESIGN: Retrospective, randomized interobserver and intraobserver comparison study of archived pathologic specimens. The study was conducted in 3 phases, and slides were evaluated blindly and independently by 5 pathologists: in phase 1, all slides were randomized and diagnosed as positive or negative. In phase 2, every third slide was evaluated again and diagnosed as positive or negative. In phase 3, slides were organized into cases, allowing evaluation of each margin in the context of the positive control (tumor from the center of the lesion) and negative control (control biopsy specimen), if available. SETTING: University referral center. STUDY MATERIAL: A total of 301 glass microscopic slides from 27 patients who underwent staged excision for lentigo maligna or lentigo maligna melanoma from March 1997 to April 2001. MAIN OUTCOME MEASURES: Interobserver and intraobserver concordance between original diagnoses and study diagnoses rendered on all slides by 5 pathologists. RESULTS: Phase 1 and 3 agreement was moderate (kappa range, 0.4-0.5). Phase 2 (intraobserver) agreement was moderate to good for all pathologists (kappa range, 0.6-0.9). Subset analysis revealed a statistically significant increase in agreement with the use of a control strip biopsy specimen for difficult slides. CONCLUSIONS: Interobserver concordance for margin analysis in lentigo maligna and lentigo maligna melanoma is moderate, and intraobserver concordance is moderate to good. A control strip biopsy specimen may improve concordance in some cases.
Adult↗
Pancreatic carcinoma surveillance in patients with familial melanoma.
OBJECTIVE: To determine the optimal methods for pancreatic adenocarcinoma surveillance in high-risk patients with familial melanoma and cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations. DESIGN: Case report with pedigree analysis and literature review, with an emphasis on guideline development for high-risk kindreds with familial pancreatic adenocarcinoma. SETTING: A university-affiliated familial melanoma research clinic. Patients The proband was referred as a participant in a research clinic protocol and was found to carry a germline CDKN2A mutation and have a history of melanoma and pancreatic adenocarcinoma. A total of 179 family members were identified through the Utah Population Database and underwent evaluation for history of melanoma and pancreatic adenocarcinoma.Intervention/ METHODS: Comprehensive family history and pedigree analysis performed by means of personal interview, medical record review, and use of cancer registry and population database records. Mutation status was confirmed by results of DNA sequence analysis. Tumor identity was confirmed with immunohistochemical markers. MAIN OUTCOME MEASURES: Estimated risk for pancreatic adenocarcinoma in a high-risk family with CDKN2A-positive melanoma. Guidelines for surveillance in these families were based on review of the literature. RESULTS: Sequence analysis confirmed a CDKN2A mutation, and immunohistochemical evaluation confirmed the diagnoses of metastatic melanoma and metastatic pancreatic adenocarcinoma. Pedigree analysis showed an observed-expected ratio of 8.9 to 12.6 for pancreatic adenocarcinoma and 16.4 to 20.8 for melanoma in this family. Guidelines used for surveillance of kindreds at high risk for pancreatic adenocarcinoma were applied to families with CDKN2A melanoma. Conclusion Patients with melanoma and a germline CDKN2A mutation should be considered for pancreatic adenocarcinoma surveillance that is based on the most recent published studies.
Adenocarcinoma↗
Lepromatous leprosy and reversal reaction in a Micronesian immigrant.
A 25-year-old Micronesian man from the island of Otia developed erythematous plaques on his legs. He was diagnosed with erythema nodosum and treated with systemic prednisone. Two months later, he presented with erythematous nodules on his forehead, cheeks, and chin (Fig. 1). Examination revealed scattered violaceous papules on his chest, arms, forearms, hands, and feet, and deep purple macules on his palms and soles. Laboratory evaluation included negative serologies for human immunodeficiency virus, rapid plasma reagin, and hepatitis A, B, and C. Routine histopathology revealed nodular aggregates of histiocytes, plasma cells, and lymphocytes. Histiocytes showed basophilic clusters of organisms within vacuoles, suggesting globi. Acid-fast stain revealed numerous acid-fast-positive rod-shaped organisms. The bacterial index on the Fite stain was four (bacterial index/Ridley's logarithmic scale, indicating 10-100 bacteria/high power field) (Fig. 2). An acid-fast stain obtained from a smear of tissue was positive for acid-fast bacilli, but no acid-fast bacilli were cultured. After the first day of treatment with dapsone 100 mg, rifampin 600 mg, and clofazimine 50 mg, the patient complained of burning and pain in his ankles and wrists. There was intense erythema within the lesions. Edema developed in his hands and feet. Consultation with the Gillis W. Long Hansen's Disease Center in Carville, Louisiana, recommended prompt treatment with corticosteroids. The edema of the hands and wrists was treated as a type I reversal reaction with prednisone 1 mg/kg/day. Subsequently, the edema and neuralgia quickly resolved in his distal extremities.
Acute-Phase Reaction↗
Novel application of a fibrin cell block method to evaluate melanocytic cell populations.
Confirming melanocytic lineage and purity is important for experiments using cultured human melanocytes. The objective of this study was to develop a simple, reliable method to evaluate and archive cultured melanocytic cells. Melanocytes were isolated from adult skin biopsies or from neonatal foreskins using standard culturing methods. Fibrin cell blocks (FCBs) were prepared from cultured cells at passages two and six. Fibrin blocks were paraffin-embedded and sectioned for immunohistochemical (CD68, Melan-A, and HMB-45) and H & E staining. Flow cytometry was performed (Melan-A) at passage six. A mixing experiment with cultured melanocytes and fibroblasts was performed and cell population purity was determined by manual counts of positively staining cells in the FCBs and by flow cytometry. The FCB method of evaluating population purity was validated experimentally and by correlation with flow cytometry results. Preparation of a FCB followed by immunohistochemical staining is an easy and inexpensive way to confirm melanocytic lineage, estimate population purity, and provide a permanent archive of cultured cells.
Adult↗
Induction of dramatic hyperpigmentation in a patient with generalized lichen planus treated with re-PUVA.
BACKGROUND: Retinoids plus PUVA (re-PUVA) may be used in the treatment of lichen planus in cases that do not respond to monotherapy. Hyperpigmentation is a potential side effect of re-PUVA therapy. OBJECTIVE: A case of remarkably intense transient hyperpigmentation secondary to re-PUVA therapy is presented. METHODS AND RESULTS: An 18-year-old male with lichen planus who had been taking isotretinoin 80 mg per day for seven days developed an exaggerated hyperpigmentation following the third dose of PUVA. CONCLUSION: As the hyperpigmentary reaction did not occur until the third PUVA dose, which was near the steady state of isotretinoin, this case may illustrate a case of photosensitization secondary to isotretinoin alone or isotretinoin in combination.
Adolescent↗
Failure to detect differences in proliferation status of nevi from CDKN2A mutation carriers and non-carriers.
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Cell Division↗