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1.
J Am Acad Dermatol ; 88(5): 1051-1059, 2023 05.
Article in English | MEDLINE | ID: mdl-31306728

ABSTRACT

BACKGROUND: Compared with sun-exposed melanomas, less is known regarding the pathogenesis of sun-protected melanomas. Sun-protected melanomas share many epidemiologic factors, but their genetic heterogeneity is not well studied. OBJECTIVE: We investigated the genomic profile of acral, mucosal, and vulvovaginal melanomas. We hypothesize that mucosal melanomas, recognized for their uniquely aggressive clinical behavior, have distinct genomic features. METHODS: We performed whole transcriptome messenger RNA and DNA (1711 genes) sequencing, messenger RNA expression profiling, tumor mutational burden, ultraviolet signature, and copy number variants analysis on 29 volar/digital acral, 7 mucosal, and 6 vulvovaginal melanomas. RESULTS: There was significant genetic heterogeneity, particularly in acral melanomas, with 36% having BRAF alterations, whereas other melanomas had none (P = .0159). Nonzero ultraviolet signatures were more frequent in acral melanomas, suggesting greater ultraviolet involvement. Mucosal melanomas formed a distinct group with increased expression of cell cycle and proliferation genes. Various targetable aberrations were identified, such as AURKA and ERBB2, in mucosal and acral melanomas, respectively. LIMITATIONS: The sample size was a small. CONCLUSION: There is significant genetic heterogeneity among sun-protected melanomas. Mucosal melanomas have upregulation in cell cycle and proliferation genes, which may explain their aggressive behavior. Ultraviolet radiation plays some role in a subset of acral but not other melanomas.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Ultraviolet Rays/adverse effects , Retrospective Studies , Mutation , Melanoma/pathology , Skin Neoplasms/pathology , Genomics , Melanoma, Cutaneous Malignant
2.
Graefes Arch Clin Exp Ophthalmol ; 260(6): 1915-1921, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34851464

ABSTRACT

PURPOSE: To report long-term fluorescein angiography (FA) findings in consecutive patients with type 1 retinopathy of prematurity (ROP) treated with intravitreal bevacizumab (IVB), whose ROP seemed to have resolved clinically. METHODS: Data were retrospectively collected for all patients with IVB-treated type 1 ROP who underwent an exam under anesthesia (EUA) and FA at 60 weeks post-gestational age (PGA) or older at a tertiary medical center between 2011 and 2020. FA results were reviewed for pathological vascular findings. RESULTS: Twenty-nine eyes of 16 patients were included. Mean gestational age and birth weight were 25.3 ± 1.5 weeks and 762.2 ± 189.8 g, respectively. The mean age at the time of EUA and FA was 23.4 ± 15.8 months. All eyes had a peripheral avascular zone and irregular peripheral branching. Vascular loops were seen in 27 eyes (93.1%) and vascular bulbs and anastomoses in 16 eyes each (55.2%). Additional abnormal findings included leakage (10 eyes, 34.5%), vessels crossing the fovea (5 eyes, 17.2%), tortuous arteries and veins (9 eyes, 31%, and 5 eyes, 17.2%, respectively), and neovascularization (2 eyes, 6.9%). When comparing patients who were less than or greater than 70 weeks PGA at follow-up, FA findings in the group with shorter follow-up were significant for more anastomoses and vascular bulbs (p = 0.002 and p = 0.024, respectively) and trended towards more leakage (45.5% vs. 27.8%, p = 0.331). CONCLUSION: The vast majority of IVB-treated type 1 ROP eyes suffered from vascular pathologies long after treatment. There may be long-term progression in the vascularization process of the retina in some cases.


Subject(s)
Retinopathy of Prematurity , Humans , Infant, Newborn , Angiogenesis Inhibitors , Bevacizumab , Gestational Age , Intravitreal Injections , Laser Coagulation , Retina/pathology , Retinal Vessels/pathology , Retinopathy of Prematurity/diagnosis , Retinopathy of Prematurity/drug therapy , Retinopathy of Prematurity/surgery , Retrospective Studies
3.
Mod Pathol ; 34(2): 348-357, 2021 02.
Article in English | MEDLINE | ID: mdl-32862201

ABSTRACT

The presence of a characteristic chimeric fusion as the initiating genomic event is one defining feature of Spitz neoplasms. Characterization of specific subtypes of Spitz neoplasms allows for better recognition facilitating diagnosis. Data on clinical outcomes of the specific tumor types may help in predicting behavior. In this study we present the largest series to date on ROS1 fusion Spitz neoplasms. We present the clinical, morphologic, and genomic features of 17 cases. We compared the morphologic features of these 17 cases to a cohort of 99 other non-ROS1 Spitz neoplasms to assess for features that may have high specificity for ROS1 fusions. These tumors consisted of ten Spitz nevi and seven Spitz tumors. None of the cases met criteria for a diagnosis of Spitz melanoma. Morphologically, the ROS1 fusion tumors of this series were characterized by a plaque-like or nodular silhouette, often densely cellular intraepidermal melanocyte proliferation, frequent pagetosis, tendency toward spindle cell cytomorphology, low grade nuclear atypia, and floating nests with occasional transepidermal elimination. However, there was a significant range in microscopic appearances, including two cases with morphologic features of a desmoplastic Spitz nevus. Different binding partners to ROS1 were identified with PWWP2A and TPM3 being the most common. No case had a recurrence or metastasis. Our findings document that most ROS1 fusion Spitz neoplasms have some typical characteristic microscopic features, while a small proportion will have features overlapping with other genomic subtypes of Spitz neoplasms. Preliminary evidence suggests that they tend to be indolent or low grade neoplasms.


Subject(s)
Nevus, Epithelioid and Spindle Cell/genetics , Nevus, Epithelioid and Spindle Cell/pathology , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Oncogene Fusion/genetics , Oncogene Proteins, Fusion/genetics
4.
Am J Dermatopathol ; 43(4): 243-251, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33742998

ABSTRACT

ABSTRACT: Two distinct studies have shown that RET fusions are found in 3%-4% of Spitz neoplasms. RET fusions have been well described in papillary thyroid cancer, non-small-cell lung cancer, breast cancer, and soft-tissue mesenchymal tumors as well as some other neoplasms. However, there are no comprehensive descriptions to date of the characteristic morphologic, clinical, or genomic findings in RET fusion Spitz neoplasms. In this study, we identified 5 cases of RET fusion Spitz neoplasms. These tumors showed characteristic morphologic features which included plaque-like silhouette and monotonous epithelioid cytology with expansile and dyscohesive nesting. Four of 5 patients including 1 diagnosed as Spitz melanoma had clinical follow-up all of which was uneventful. Furthermore, we describe the genomic sequences in 4 of these cases, 2 of which have previously described KIF5B-RET fusion and 2 of which had a novel LMNA-RET fusion. We believe this report significantly contributes to our current knowledge regarding Spitz neoplasms and describes characteristics features which can help with recognition of the RET subgroup of Spitz.


Subject(s)
Biomarkers, Tumor/genetics , Gene Fusion , Melanocytes/pathology , Melanoma/genetics , Nevus, Epithelioid and Spindle Cell/genetics , Proto-Oncogene Proteins c-ret/genetics , Skin Neoplasms/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , Comparative Genomic Hybridization , Databases, Factual , Female , Genetic Predisposition to Disease , Humans , In Situ Hybridization, Fluorescence , Infant , Male , Melanoma/pathology , Middle Aged , Nevus, Epithelioid and Spindle Cell/pathology , Phenotype , Retrospective Studies , Skin Neoplasms/pathology , Young Adult
5.
J Am Acad Dermatol ; 83(4): 1028-1034, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32446823

ABSTRACT

BACKGROUND: Atypical network encompasses several patterns. Few studies assess the sensitivity, specificity, and positive and negative predictive values of network subtypes. OBJECTIVE: We assessed the diagnostic value of atypical network subtypes and their histopathologic correlates in cutaneous melanocytic lesions. METHODS: A retrospective search (2014-2018) from a high-risk melanoma clinic for cases scored for atypical network with accompanying dermoscopic photographs yielded 120 lesions (15 melanoma; 30 severely, 38 moderately, and 32 mildly atypical nevi; 4 compound nevi; and 1 junctional nevus). A dermatopathologist blinded to diagnosis assessed dermoscopic and histologic features. Network abnormality correlates with histopathology and clinical diagnoses were assessed with sensitivity, specificity, positive and negative predictive values, and odds ratios. RESULTS: A multivariable model with shiny white streaks (odds ratio 3.02) and inverse network (OR 4.46) was most predictive of melanoma or severe atypia. Positive predictive value for melanoma or severe atypia in decreasing order was inverse network (73.9%), shiny white streaks (71.4%), loss of network (46%), branched streaks (29.4%), and thick brown lines (28.4%). LIMITATIONS: Cases were retrospectively found from a pigmented lesion clinic and evaluated by a single dermatopathologist. CONCLUSION: Shiny white streaks and inverse network are most predictive of melanoma or severe atypia and warrant biopsy if found on dermoscopy.


Subject(s)
Dysplastic Nevus Syndrome/diagnostic imaging , Melanoma/diagnostic imaging , Nevus, Pigmented/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Adult , Aged , Dermoscopy , Dysplastic Nevus Syndrome/pathology , Female , Humans , Male , Melanoma/pathology , Middle Aged , Nevus, Pigmented/pathology , Predictive Value of Tests , Retrospective Studies , Skin Neoplasms/pathology , Young Adult
6.
J Cutan Pathol ; 47(12): 1132-1142, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32776349

ABSTRACT

BACKGROUND: Fusions involving the BRAF gene are responsible for 5% of Spitz neoplasms. To better characterize them, we report the clinical, morphological, and genomic findings of six BRAF fusion Spitz tumors. METHODS: The morphological, clinical, and molecular findings of six BRAF fusion Spitz neoplasms assessed by next generation sequencing (NGS) were compared to a control set of Spitz without BRAF fusions. RESULTS: BRAF fusion Spitz tumors had frequent predominance of epithelioid morphology (4/6 cases), frequent high-grade nuclear atypia and pleomorphism (5/6 cases), and a frequent desmoplastic base (3/6 cases). Five of six cases were diagnosed as atypical Spitz tumor and one as Spitz nevus. All cases had uneventful clinical follow-up. There were five different fusion partners, with CLIP2 being the most frequent. Secondary pathogenic mutations were frequent and chromosomal copy number changes were seen in three of six cases by an NGS platform. CONCLUSIONS: BRAF fusions Spitz usually have epithelioid morphology, high-grade nuclear atypia, and desmoplasia. Chromosomal copy number changes are not infrequent. While our cases had uneventful follow-up, a meta-analysis of the literature suggests that among the fusion subtypes associated with Spitz tumors, they are among the subgroups more likely to develop distant metastasis.


Subject(s)
Dysplastic Nevus Syndrome/genetics , Nevus, Epithelioid and Spindle Cell/genetics , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/pathology , Adult , Aged , Case-Control Studies , Child , Dysplastic Nevus Syndrome/diagnosis , Dysplastic Nevus Syndrome/pathology , Female , Genomics/methods , High-Throughput Nucleotide Sequencing/methods , Humans , Male , Microtubule-Associated Proteins/genetics , Mutation , Nevus, Epithelioid and Spindle Cell/diagnosis , Nevus, Epithelioid and Spindle Cell/pathology , Oncogene Proteins, Fusion/genetics , Retrospective Studies , Skin Neoplasms/ultrastructure
7.
Am J Dermatopathol ; 42(9): 641-647, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32000215

ABSTRACT

BACKGROUND: Some melanomas closely resemble pigmented spindle cell nevi (PSCN) of Reed histologically. The distinction of these entities is important for clinical management. A recent study showed most PSCN (78%) are fusion-driven, commonly involving NTRK3 (57%). Conversely, BRAF V600E mutations are not characteristic of PSCN but are frequent in melanoma. OBJECTIVE: In this study, we assessed clinical, histologic and genomic differences between PSCN of Reed and Reed-like melanomas (RLMs). METHODS: We performed BRAF V600E immunohistochemistry (IHC) for 18 PSCN and 20 RLM cases. All 23 benign PSCN cases previously underwent whole transcriptome and targeted DNA sequencing with a 1711 gene panel. RESULTS: We previously demonstrated the majority of PSCN (18 of 23) has chimeric fusions. Among PSCN without a chimeric fusion, BRAF mutations were common. Noncanonical BRAF mutations were identified in 2 of 5 nonfusion cases, and 1 case had a canonical BRAF mutation. Alternatively, 70% of RLM demonstrated a BRAF V600E mutation. RLM also occurred more frequently in older patients. LIMITATIONS: The overall sample size was small. CONCLUSIONS: In diagnostically challenging cases, ancillary IHC studies can assist in distinguishing PSCN from RLM. Our study suggests positive staining by IHC for BRAF V600E and older age strongly favors a diagnosis of RLM.


Subject(s)
Biomarkers, Tumor/genetics , Melanoma/genetics , Mutation , Nevus, Epithelioid and Spindle Cell/genetics , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/genetics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Diagnosis, Differential , Female , Genetic Predisposition to Disease , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Infant , Male , Melanoma/pathology , Middle Aged , Nevus, Epithelioid and Spindle Cell/pathology , Phenotype , Predictive Value of Tests , Retrospective Studies , Skin Neoplasms/pathology , Exome Sequencing , Young Adult
8.
J Am Acad Dermatol ; 80(3): 685-693, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30287318

ABSTRACT

BACKGROUND: Repigmentation at previous biopsy sites pose a significant diagnostic dilemma given clinical and histologic similarities between recurrent nevi and locally recurrent melanoma. Though common in melanoma, the role of TERT promoter mutations (TPMs) in recurrent nevi is unknown. OBJECTIVE: We investigated the role of TPMs in recurrent nevi and whether the presence of hotspot TPM distinguishes recurrent nevi from locally recurrent melanoma. We also characterized clinical and histologic features differentiating these lesions. METHODS: We analyzed 11 locally recurrent melanomas, 17 recurrent nevi, and melanoma and nevus controls to determine TPM status. We also assessed clinical and histologic features of the recurrent groups. RESULTS: Hotspot TPMs were more common in recurrent melanomas than recurrent nevi (P = .008). Recurrent melanomas were more likely to have solar elastosis (P = .0047), multilayering of melanocytes in the epidermis (P = .0221), adnexal involvement (P = .0069), and epidermal consumption (P = .0204). Recurrent nevi had intra-epidermal atypia limited to the area above the scar (P < .0001) and occurred earlier after the original biopsy (P < .0008). Solar elastosis, months to recurrence, and hotspot TPMs were independently associated with recurrent melanoma in multivariate analysis. LIMITATIONS: This was a retrospective study. CONCLUSION: Hotspot TPMs are significantly more frequent in recurrent melanomas and could serve as a diagnostic clue in histologically ambiguous cases.


Subject(s)
Melanoma/diagnosis , Neoplasm Recurrence, Local/diagnosis , Nevus, Pigmented/diagnosis , Promoter Regions, Genetic , Skin Neoplasms/diagnosis , Telomerase/genetics , Adult , Case-Control Studies , Diagnosis, Differential , Female , Humans , Male , Melanoma/genetics , Melanoma/pathology , Middle Aged , Mutation , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Nevus, Pigmented/genetics , Nevus, Pigmented/pathology , Retrospective Studies , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Time Factors
9.
J Am Acad Dermatol ; 80(6): 1585-1593, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30244062

ABSTRACT

BACKGROUND: Multiple BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) have been associated with a familial cancer syndrome involving germline mutations in BAP1. OBJECTIVES: We sought to describe the clinical and dermoscopic features of BIMTs. METHODS: This was a retrospective, multicenter, case-control study. Participating centers contributed clinical data, dermoscopic images, and histopathologic data of biopsy-proven BIMTs. We compared the dermoscopic features between BIMTs and control patients. RESULTS: The dataset consisted of 48 BIMTs from 31 patients (22 women; median age 37 years) and 80 control patients. Eleven patients had a BAP1 germline mutation. Clinically, most BIMTs presented as pink, dome-shaped papules (n = 24). Dermoscopically, we identified 5 patterns: structureless pink-to-tan with irregular eccentric dots/globules (n = 14, 29.8%); structureless pink-to-tan with peripheral vessels (n = 10, 21.3%); structureless pink-to-tan (n = 7, 14.9%); a network with raised, structureless, pink-to-tan areas (n = 7, 14.9%); and globular pattern (n = 4, 8.5%). The structureless with eccentric dots/globules pattern and network with raised structureless areas pattern were only identified in BIMT and were more common in patients with BAP1 germline mutations (P < .0001 and P = .001, respectively). LIMITATIONS: Limitations included our small sample size, retrospective design, the absence of germline genetic testing in all patients, and inclusion bias toward more atypical-looking BIMTs. CONCLUSIONS: Dome-shaped papules with pink-to-tan structureless areas and peripheral irregular dots/globules or network should raise the clinical suspicion for BIMT.


Subject(s)
Melanoma/pathology , Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Adolescent , Adult , Aged , Biopsy , Case-Control Studies , Child , Databases, Factual , Dermoscopy , Female , Germ-Line Mutation , Humans , Male , Melanoma/genetics , Middle Aged , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Neoplastic Syndromes, Hereditary/genetics , Nevus, Epithelioid and Spindle Cell/genetics , Nevus, Epithelioid and Spindle Cell/pathology , Nevus, Pigmented/genetics , Observer Variation , Retrospective Studies , Sample Size , Single-Blind Method , Skin Neoplasms/genetics , Young Adult
10.
J Cutan Pathol ; 46(11): 878-887, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31152596

ABSTRACT

Recent advances in next generation sequencing (NGS) have allowed for efficient whole transcriptome sequencing, leading to the identification of important kinase fusions as the primary driver in some melanocytic neoplasms. These fusions typically occur mutually exclusively of one another and other well-known initiating mutations such as BRAF, NRAS, NF1, KIT, and GNAQ. Fusions are found in over 50% of Spitz neoplasms, including ALK, BRAF, NTRK1, NTRK3, ROS1, MET, MAP3K8, and RET. Familiarity with the typical morphologic features of certain fusion-driven melanocytic neoplasms can help with classification, diagnosis, and identification of targeted molecular therapies in malignant cases. Spitz tumors with ALK, NTRK1, and NTRK3 fusions have characteristic morphologic features. BRAF and MAP3K8 fusions, in particular, tend to be epithelioid, high grade, and more frequent in Spitz melanoma than other fusion subtypes. Sporadic cases of pigmented epithelioid melanocytoma may have PRKCA fusions and sheets of monomorphic epithelioid melanocytes. Fusion events are also enriched among melanomas without the key mutations BRAF, NRAS, or NF1. Although NGS is the most reliable method to detect fusions, immunohistochemistry and fluorescence in situ hybridization are cost-effective alternatives in some cases. We describe recent discoveries regarding the role of kinase fusions in melanocytic neoplasms and their associated morphologies.


Subject(s)
Gene Fusion , Melanoma , Mutation , Nevus, Epithelioid and Spindle Cell , Oncogene Proteins, Fusion , Skin Neoplasms , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry , Melanoma/genetics , Melanoma/metabolism , Melanoma/pathology , Nevus, Epithelioid and Spindle Cell/genetics , Nevus, Epithelioid and Spindle Cell/metabolism , Nevus, Epithelioid and Spindle Cell/pathology , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Skin Neoplasms/pathology
13.
J Am Acad Dermatol ; 79(3): 525-534, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29753057

ABSTRACT

BACKGROUND: BRCA1-associated protein 1 (BAP1)-inactivated melanocytic tumors (BIMTs) are often the earliest sign of the BAP1 tumor predisposition syndrome. Identification of BIMTs and selection of patients for germline testing affect the lives of patients with germline BAP1 mutations. OBJECTIVE: To describe the spectrum of histomorphologic findings in BAP1-inactivated melanocytic lesions to improve their recognition. We determined the frequency of sporadic versus germline cases in our cohort, assessing whether any features were statistically linked to germline status. METHODS: Histomorphologic features of BAP1-inactivated melanocytic lesions were analyzed by comparing cases with germline mutations with those with unknown or negative status. Available clinical follow-up data were reported. RESULTS: The histomorphologic spectrum of BAP1-inactivated melanocytic lesions is broad; it includes cases with spitzoid cytomorphology (69%), smaller epithelioid cells without spitzoid features (31%), and rhabdoid cytologic features (58%). BIMTs from patients with germline mutations were statistically more likely to have an extensive junctional component of BAP1-inactivated melanocytes (P = .0177). All 11 patients with suspected or confirmed germline mutations had a history of cutaneous melanoma or multiple BIMTs. LIMITATIONS: The unknown germline status of 77 patients. CONCLUSION: Approximately 12% of patients with BIMTs have germline mutations. Extensive junctional involvement in a BIMT and a personal history of melanoma or previous BIMT may be additional indications for germline testing.


Subject(s)
Genetic Testing , Melanoma/genetics , Neoplasms, Multiple Primary/genetics , Nevus, Pigmented/genetics , Skin Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Adult , Female , Germ-Line Mutation , Humans , Male , Medical History Taking , Melanoma/metabolism , Melanoma/pathology , Neoplasms, Multiple Primary/metabolism , Neoplasms, Multiple Primary/pathology , Nevus, Pigmented/metabolism , Nevus, Pigmented/pathology , Patient Selection , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Tumor Suppressor Proteins/metabolism , Ubiquitin Thiolesterase/metabolism
14.
J Am Acad Dermatol ; 78(5): 913-919, 2018 05.
Article in English | MEDLINE | ID: mdl-29138058

ABSTRACT

BACKGROUND: Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi. OBJECTIVE: We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions. METHODS: Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation. RESULTS: Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P < .001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P = .009), and SWSs correlated with greater Breslow depth among melanomas (P = .007). LIMITATIONS: This study was retrospective. CONCLUSION: Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma.


Subject(s)
Dermoscopy/methods , Melanoma/pathology , Nevus, Pigmented/pathology , Skin Neoplasms/pathology , Adult , Aged , Biopsy, Needle , Case-Control Studies , Diagnosis, Differential , Dysplastic Nevus Syndrome/diagnosis , Dysplastic Nevus Syndrome/pathology , Female , Humans , Immunohistochemistry , Male , Melanocytes/pathology , Melanoma/diagnosis , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Nevus, Epithelioid and Spindle Cell/diagnosis , Nevus, Epithelioid and Spindle Cell/pathology , Nevus, Pigmented/diagnosis , Retrospective Studies , Skin Neoplasms/diagnosis
15.
Am J Surg Pathol ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864210

ABSTRACT

Tumors morphologically classified as pigmented epithelioid melanocytomas (PEMs) are genomically diverse, with the 2 most common genomic subtypes being PRKC fusions or PRKAR1A inactivating mutations. PRKC fusions activate the Gαq/11 pathway similar to blue nevi. Conversely, inactivating mutations in PRKAR1A activate the Gαs pathway. We hypothesize that PRKC fusions have greater genomic overlap with blue nevi compared with PRKAR1A-inactivated PEMs. We characterized the clinical and morphologic features of 21 PRKC and PRKACB fusion melanocytic tumors and compared this to PRKAR1A mutated PEMs. To test our hypothesis regarding greater genomic overlap between PRKC fusions and blue nevi relative to PRKAR1A mutated PEMs, we performed a principal component analysis (PCA) using mRNA expression data. Lastly, we performed a meta-analysis focusing on the outcome data of PRKC fusions. PRKC fusions occur at a younger median age than PRKAR1A mutated PEMs (16 vs. 27). Histologically, PRKC fusions have solid aggregates of epithelioid melanocytes not typical of PRKAR1A mutated PEMs. The PCA plot showed no overlap between the PRKC fusion group and the PRKAR1A-mutated PEMs. There was a significant overlap between PRKC fusions and blue nevi. A meta-analysis of PRKC fusion cases in the literature suggests melanoma is uncommon, but the loss of BAP-1 nuclear expression may be associated with an adverse prognosis as in tumors from the blue nevus family. PRKC fusion melanocytic tumors have greater genomic overlap with blue nevi compared with PRKAR1A mutated PEMs. We recommend categorizing benign PRKC fusion melanocytic tumors as blue fusion nevi/tumors.

16.
Antimicrob Agents Chemother ; 57(1): 552-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23147721

ABSTRACT

Chlorhexidine and mupirocin are used in health care facilities to eradicate methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of this study was to assess the frequency of chlorhexidine and mupirocin resistance in isolates from nares carriers in multiple nursing homes and to examine characteristics associated with resistance. Nasal swab samples were collected from approximately 100 new admissions and 100 current residents in 26 nursing homes in Orange County, CA, from October 2008 to May 2011. MRSA isolates were tested for susceptibility by using broth microdilution, disk diffusion, and Etest; for genetic relatedness using pulsed-field gel electrophoresis; and for qac gene carriage by PCR. Characteristics of the nursing homes and their residents were collected from the Medicare Minimum Data Set and Long-Term Care Focus. A total of 829 MRSA isolates were obtained from swabbing 3,806 residents in 26 nursing homes. All isolates had a chlorhexidine MIC of ≤4 µg/ml. Five (0.6%) isolates harbored the qacA and/or qacB gene loci. Mupirocin resistance was identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%. None of the isolates with HLMR displayed qacA or qacB, while two isolates carried qacA and exhibited low-level mupirocin resistance. Detection of HLMR was associated with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P = 0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly one-third of MRSA isolates. These findings may have implications for the increasingly widespread practice of MRSA decolonization using intranasal mupirocin.


Subject(s)
Anti-Bacterial Agents/pharmacology , Chlorhexidine/pharmacology , Disinfectants/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Mupirocin/pharmacology , Staphylococcal Infections/microbiology , Aged , Aged, 80 and over , Bacterial Proteins/genetics , Carrier State , Drug Resistance, Bacterial , Electrophoresis, Gel, Pulsed-Field , Female , Humans , Long-Term Care , Male , Membrane Transport Proteins/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Nasal Cavity/drug effects , Nasal Cavity/microbiology , Nursing Homes , Polymerase Chain Reaction
17.
J Clin Microbiol ; 51(11): 3788-95, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24025901

ABSTRACT

Nursing homes represent a unique and important methicillin-resistant Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from hospitals and the community, strains can be transported back into these settings from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet relatively poorly studied in this setting, a multicenter, regional assessment of the frequency and diversity of MRSA in the nursing home reservoir was carried out and compared to that of the MRSA from hospitals in the same region. The prospective study collected MRSA from nasal swabbing of residents of 26 nursing homes in Orange County, California, and characterized each isolate by spa typing. A total of 837 MRSA isolates were collected from the nursing homes. Estimates of admission prevalence and point prevalence of MRSA were 16% and 26%, respectively. The spa type genetic diversity was heterogeneous between nursing homes and significantly higher overall (77%) than the diversity in Orange County hospitals (72%). MRSA burden in nursing homes appears largely due to importation from hospitals. As seen in Orange County hospitals, USA300 (sequence type 8 [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant MRSA clones in Orange County nursing homes, representing 83% of all isolates, although the USA100 variant was predominant in nursing homes, whereas USA300 was predominant in hospitals. Control strategies tailored to the complex problem of MRSA transmission and infection in nursing homes are needed in order to minimize the impact of this unique reservoir on the overall regional MRSA burden.


Subject(s)
Genetic Variation , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Aged , Aged, 80 and over , California/epidemiology , Female , Genotype , Hospitals , Humans , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Molecular Epidemiology , Molecular Typing , Nasal Cavity/microbiology , Nursing Homes , Prevalence , Prospective Studies , Staphylococcal Protein A/genetics
18.
Am J Clin Dermatol ; 24(5): 675-680, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37328613

ABSTRACT

As research related to skin of color (SOC) in dermatology continues to grow, it is increasingly important to precisely define terminology. The terms 'SOC', 'race', and 'ethnicity' are frequently used to analyze differences in dermatologic disease onset, severity, and outcomes. These terms are used interchangeably, are ill-defined across research studies, and frequently conflate biologic and socially constructed categories. SOC has been thought to represent differing degrees of pigment or melanin in the skin, however skin pigment is quite variable among races and ethnicities. Furthermore, certain individuals with less skin pigment may socially consider themselves to be SOC, while the inverse is also true. Fitzpatrick skin phototype classifications in SOC dermatology, while commonly used as an objective measure of diversity, also present with numerous limitations and inaccuracies. We seek to highlight strengths and weaknesses of the current terminology used in SOC dermatology and recommend a more holistic understanding of reported differences, including a framework reflective of upstream socioeconomic, environmental, and historical factors that may be most relevant to reported associations.


Subject(s)
Dermatology , Pigmentation Disorders , Humans , Skin , Skin Pigmentation , Ethnicity
19.
Am J Clin Dermatol ; 24(5): 731-751, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37336869

ABSTRACT

Atopic dermatitis (AD) is a chronic, heterogeneous inflammatory skin disease that is associated with immense patient burden globally. There is increasing appreciation of disparities among patients identified as having skin of color (SOC), which often refers to patients of non-White race or non-European ancestry, but can broadly include individuals from a number of different racial, ethnic, ancestral, and skin pigmentation groups based on definition. In this narrative review, we discuss key terminology as it relates to AD across shades of skin, including modern definitions of 'race', 'ethnicity', and 'SOC'. We then synthesize the current literature describing disparities in AD prevalence, disease recognition, and burden alongside current data regarding genetic and immunologic findings across SOC populations. In the context of these findings, we highlight key concomitant social determinants of health, including environmental factors, socioeconomic status, and access to care, for which race often serves as a proxy for true biological and genetic differences. Finally, we discuss future efforts to shift to a more inclusive understanding of AD to encompass all shades of skin, to ensure equitable representation of diverse populations in high impact research, and intensify efforts to address the critical upstream factors driving observed disparities.


Subject(s)
Dermatitis, Atopic , Humans , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/genetics , Ethnicity/genetics , Socioeconomic Factors , Skin Pigmentation
20.
BMC Infect Dis ; 12: 269, 2012 Oct 24.
Article in English | MEDLINE | ID: mdl-23095678

ABSTRACT

BACKGROUND: MRSA prevalence in nursing homes often exceeds that in hospitals, but reasons for this are not well understood. We sought to measure MRSA burden in a large number of nursing homes and identify facility characteristics associated with high MRSA burden. METHODS: We performed nasal swabs of residents from 26 nursing homes to measure MRSA importation and point prevalence, and estimate transmission. Using nursing home administrative data, we identified facility characteristics associated with MRSA point prevalence and estimated transmission risk in multivariate models. RESULTS: We obtained 1,649 admission and 2,111 point prevalence swabs. Mean MRSA point prevalence was 24%, significantly higher than mean MRSA admission prevalence, 16%, (paired t-test, p<0.001), with a mean estimated MRSA transmission risk of 16%.In multivariate models, higher MRSA point prevalence was associated with higher admission prevalence (p=0.005) and higher proportions of residents with indwelling devices (p=0.01). Higher estimated MRSA transmission risk was associated with higher proportions of residents with diabetes (p=0.01) and lower levels of social engagement (p=0.03). CONCLUSIONS: MRSA importation was a strong predictor of MRSA prevalence, but MRSA burden and transmission were also associated with nursing homes caring for more residents with chronic illnesses or indwelling devices. Frequent social interaction among residents appeared to be protective of MRSA transmission, suggesting that residents healthy enough to engage in group activities do not incur substantial risks of MRSA from social contact. Identifying characteristics of nursing homes at risk for high MRSA burden and transmission may allow facilities to tailor infection control policies and interventions to mitigate MRSA spread.


Subject(s)
Cross Infection/epidemiology , Cross Infection/transmission , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Nursing Homes , Staphylococcal Infections/epidemiology , Staphylococcal Infections/transmission , Adolescent , Adult , Aged , Aged, 80 and over , Carrier State/epidemiology , Carrier State/microbiology , Carrier State/transmission , Child , Child, Preschool , Cross Infection/microbiology , Female , Humans , Infant , Male , Middle Aged , Nose/microbiology , Risk Factors , Staphylococcal Infections/microbiology , Young Adult
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