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1.
Am J Dermatopathol ; 46(6): 337-345, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38133527

RESUMO

INTRODUCTION: Although many individual cases and small series of toxic erythema of chemotherapy (TEC) have been described, the full spectrum of findings is not well understood. OBJECTIVE: To provide a comprehensive review of the clinical and histopathologic features of TEC with an emphasis on novel histopathologic findings. METHODS: We searched our electronic medical record for "toxic erythema of chemotherapy" or "neutrophilic eccrine hidradenitis." Fifty-six cases meeting clinical and histopathologic criteria were identified. The electronic medical record and accompanying hematoxylin and eosin-stained slides were retrospectively reviewed. RESULTS: The clinical findings were heterogeneous but included classic presentations such as intertriginous eruptions (34%) and acral erythema (25%). The most common histopathologic features were apoptotic keratinocytes (95%), basal vacuolar change (91%), and epithelial dysmaturation (79%). Eccrine squamous syringometaplasia was seen in over half of the cases (33/56; 59%), whereas neutrophilic eccrine hidradenitis was uncommon (16%). Interestingly, many cases showed prominent interstitial histiocytes (55%). Other novel findings included irregular orthohyperkeratosis (23%), irregular epidermal hyperplasia (14%), and acantholysis (9%). LIMITATIONS: As a retrospective study, it is subject to information bias. CONCLUSION: This is the largest reported series of TEC. In addition to confirming previously reported features, we identify novel histopathologic findings to add to the spectrum of TEC.


Assuntos
Antineoplásicos , Toxidermias , Eritema , Humanos , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Masculino , Toxidermias/patologia , Toxidermias/etiologia , Idoso , Adulto , Antineoplásicos/efeitos adversos , Eritema/induzido quimicamente , Eritema/patologia , Adulto Jovem , Hidradenite/induzido quimicamente , Hidradenite/patologia , Idoso de 80 Anos ou mais
2.
J Cutan Pathol ; 50(7): 637-641, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37062590

RESUMO

Cutaneous mucormycosis may be caused by direct inoculation or hematogenous spread of mucormycetes in immunocompromised patients. Skin biopsy is characterized by a deep fungal infection with frequent angioinvasion. The fungal hyphae can usually be identified on H&E stain. We report a case of cutaneous angioinvasive mucormycosis in which the fungi were also visualized on direct immunofluorescence. A 57-year-old patient with relapsed myelodysplastic syndrome status-post allogeneic hematopoietic cell transplant, diabetes mellitus, and graft-versus-host disease presented with painful, palpable, dark-red to violaceous retiform purpuric plaques. Light microscopy of punch biopsy revealed numerous broad, ribbon-like, pauci-septate hyphae in the dermis with angioinvasion, consistent with mucormycosis. Direct immunofluorescence performed on a concurrent biopsy to exclude immune complex vasculitis showed smooth IgG, IgA (weak), IgM (faint), and C3 deposition on the hyphal structures, compatible with antibody-coated fungi. Tissue culture subsequently confirmed Mucor species. Although mucormycosis was readily diagnosable on routine light microscopy in this case, recognition of the unique phenomenon of antibody-coated fungi can be crucial when the invasive fungi are sparse or only present in the direct immunofluorescence specimen.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mucormicose , Humanos , Pessoa de Meia-Idade , Mucor , Mucormicose/diagnóstico , Técnica Direta de Fluorescência para Anticorpo , Biópsia
3.
J Cutan Pathol ; 49(11): 938-942, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35734802

RESUMO

A 58-year-old woman was admitted for heart failure and concern for cardiogenic shock. The patient had been recently placed on colchicine and allopurinol, 4 months and 3 weeks, respectively, prior to admission. Upon admission, she had a cutaneous eruption that had started abruptly several days after allopurinol initiation. It included multiple erythematous papules with scant scale on the forearms and numerous erythematous papules on the legs. Because of the varied morphologic presentation, biopsies from both the thigh and forearm were performed for a suspected drug reaction. The specimen from the thigh showed a superficial-dermal, band-like lymphocytic infiltrate with dyskeratosis and numerous intraepidermal mitotic figures predominantly in metaphase. In addition, there were neutrophils with leukocytoclasia. The specimen from the forearm showed superficial perivascular lymphocytic inflammation and intraepidermal dyskeratosis with mitotic figures similar to the thigh biopsy specimen but without a dermal neutrophilic infiltrate. An unusual drug eruption with features of colchicine toxicity was favored. Colchicine toxicity is not a commonly encountered clinical scenario and cutaneous findings have only rarely been described. Herein we report an exceedingly rare case of an unusual drug reaction with "colchicine figures" (i.e., ring-shaped mitotic figures arrested in metaphase) consistent with colchicine toxicity.


Assuntos
Toxidermias , Exantema , Alopurinol/efeitos adversos , Colchicina/efeitos adversos , Toxidermias/etiologia , Eritema , Feminino , Humanos , Pessoa de Meia-Idade
4.
J Cutan Pathol ; 49(3): 299-305, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34699105

RESUMO

The DUSP22-IRF4 gene rearrangement results in downregulation of DUSP22, a presumed tumor suppressor in T-cell lymphomagenesis. It has been described in some cases of primary cutaneous and systemic anaplastic large-cell lymphoma, lymphomatoid papulosis, and transformed mycosis fungoides. Here we describe two patients with clinical lesions resembling patch/plaque mycosis fungoides that did not meet WHO criteria for large-cell transformation on histopathology yet showed a DUSP22 translocation. One patient who had a history of systemic anaplastic large-cell lymphoma with DUSP22 translocation presented with cutaneous involvement by his systemic lymphoma along with lymphomatoid papulosis and mycosis-fungoides-like lesions, all showing an identical immunophenotype and T-cell clone. These cases expand the spectrum of DUSP22-rearranged lymphomas to include mycosis-fungoides-like presentations without large-cell transformation.


Assuntos
Fosfatases de Especificidade Dupla/genética , Linfoma Cutâneo de Células T/patologia , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Rearranjo Gênico , Humanos , Linfoma Cutâneo de Células T/genética , Masculino , Neoplasias Cutâneas/genética , Translocação Genética
5.
J Cutan Pathol ; 49(3): 231-245, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34536035

RESUMO

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.


Assuntos
Dermatologia/normas , Patologia Clínica/normas , Dermatopatias/patologia , Medicina Baseada em Evidências/normas , Humanos , Sociedades Médicas , Estados Unidos
6.
Australas J Dermatol ; 63(4): e356-e359, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35866718

RESUMO

We describe a strikingly robust presentation of trimethoprim-sulfamethoxazole (TMP-SMX)-induced pustular Sweet syndrome and discuss how to distinguish it from iododerma and other neutrophil-rich conditions. A review of the literature indicates that TMP-SMX-induced Sweet syndrome (SS) may have higher rates of neutrophilia and greater ocular, mucosal, and musculoskeletal involvement compared to SS from other drugs. Recognizing these features and identifying the offending agent are critical for correctly diagnosing TMP-SMX-induced SS in a timely manner.


Assuntos
Síndrome de Sweet , Combinação Trimetoprima e Sulfametoxazol , Humanos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Síndrome de Sweet/induzido quimicamente , Síndrome de Sweet/diagnóstico
7.
Carcinogenesis ; 42(8): 1100-1109, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34117865

RESUMO

Uncontrolled activation of the Hedgehog (Hh) signaling pathway, operating through GLI transcription factors, plays a central role in the pathogenesis of cutaneous basal cell carcinoma and contributes to the development of several malignancies arising in extracutaneous sites. We now report that K5-tTA;tetO-Gli2 bitransgenic mice develop distinctive epithelial tumors within their jaws. These tumors consist of large masses of highly proliferative, monomorphous, basaloid cells with scattered foci of keratinization and central necrosis, mimicking human basaloid squamous cell carcinoma (BSCC), an aggressive upper aerodigestive tract tumor. Like human BSCC, these tumors express epidermal basal keratins and differentiation-specific keratins within squamous foci. Mouse BSCCs express high levels of Gli2 and Hh target genes, including Gli1 and Ptch1, which we show are also upregulated in a subset of human BSCCs. Mouse BSCCs appear to arise from distinct epithelial sites, including the gingival junctional epithelium and epithelial rests of Malassez, a proposed stem cell compartment. Although Gli2 transgene expression is restricted to epithelial cells, we also detect striking alterations in bone adjacent to BSCCs, with activated osteoblasts, osteoclasts and osteal macrophages, indicative of active bone remodeling. Gli2 transgene inactivation resulted in rapid BSCC regression and reversal of the bone remodeling phenotype. This first-reported mouse model of BSCC supports the concept that uncontrolled Hh signaling plays a central role in the pathogenesis of a subset of human BSCCs, points to Hh/GLI2 signaling as a potential therapeutic target and provides a powerful new tool for probing the mechanistic underpinnings of tumor-associated bone remodeling.


Assuntos
Remodelação Óssea , Carcinoma de Células Escamosas/patologia , Proteínas Hedgehog/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Cutâneas/patologia , Proteína Gli2 com Dedos de Zinco/metabolismo , Animais , Carcinoma de Células Escamosas/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Neoplasias Cutâneas/metabolismo
8.
J Cutan Pathol ; 48(7): 986-994, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33856064

RESUMO

Primary cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of neoplasms with variable clinical behavior. Immunophenotypic switch (IS) is a phenomenon that occurs during lymphoma progression and is defined by an alteration in the immunophenotypic expression of a tumor with retention of its genotypic signature. This has been well-recognized in hematopoietic neoplasms; however, it has been rarely reported in CTCL and its clinical implications are not well understood. We present the clinical, histopathologic, immunophenotypic, and genetic findings of three cases of CTCL that demonstrated IS post treatment with variable outcomes. We add our cases to the small number previously reported to increase awareness of this phenomenon and its diagnostic challenge.


Assuntos
Transformação Celular Neoplásica/imunologia , Imunofenotipagem/métodos , Linfoma Cutâneo de Células T/diagnóstico , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conscientização , Biópsia/métodos , Transformação Celular Neoplásica/patologia , Pré-Escolar , Diagnóstico Diferencial , Progressão da Doença , Evolução Fatal , Feminino , Rearranjo Gênico/genética , Genes Codificadores dos Receptores de Linfócitos T/genética , Genótipo , Humanos , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/imunologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/tratamento farmacológico , Micose Fungoide/metabolismo , Micose Fungoide/radioterapia , Neoplasias Cutâneas/imunologia , Resultado do Tratamento
9.
Mod Pathol ; 33(6): 1092-1103, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31857679

RESUMO

Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its infiltrative growth and histopathologic overlap with benign adnexal tumors, often posing challenges to both diagnosis and management. Understanding the molecular underpinnings of microcystic adnexal carcinoma may allow for more accurate diagnosis and identify potential targetable oncogenic drivers. We characterized 18 microcystic adnexal carcinomas by targeted, multiplexed PCR-based DNA next-generation sequencing of the coding sequence of over 400 cancer-relevant genes. The majority of cases had relatively few (<8) prioritized somatic mutations, and lacked an ultraviolet (UV) signature. The most recurrent mutation was TP53 inactivation in four (22%) tumors. Frame-preserving insertions affecting the kinase domain of JAK1 were detected in three (17%) cases, and were nonoverlapping with TP53 mutations. Seven (39%) cases demonstrated copy number gain of at least one oncogene. By immunohistochemistry, p53 expression was significantly higher in microcystic adnexal carcinomas with TP53 mutations compared with those without such mutations and syringomas. Similarly, phospho-STAT3 expression was significantly higher in microcystic adnexal carcinomas harboring JAK1 kinase insertions compared with those with wild-type JAK1 and syringomas. In conclusion, microcystic adnexal carcinomas are molecularly heterogeneous tumors, with inactivated p53 or activated JAK/STAT signaling in a subset. Unlike most other nonmelanoma skin cancers involving sun-exposed areas, most microcystic adnexal carcinomas lack evidence of UV damage, and hence likely originate from a relatively photo-protected progenitor population in the dermis. These findings have implications for the biology, diagnosis, and treatment of microcystic adnexal carcinomas, including potential for therapeutic targeting of p53 or the JAK/STAT pathway in advanced tumors.


Assuntos
Carcinoma/genética , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/fisiologia , Neoplasias das Glândulas Sudoríparas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma/metabolismo , Carcinoma/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fosforilação , Neoplasias das Glândulas Sudoríparas/metabolismo , Neoplasias das Glândulas Sudoríparas/patologia , Proteína Supressora de Tumor p53/metabolismo
10.
Mod Pathol ; 33(7): 1307-1317, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32066860

RESUMO

Increasingly, molecular methods are being utilized in the workup of melanocytic neoplasms. To this end, we sought to correlate data from a single nucleotide polymorphism (SNP) array platform based on molecular inversion probes with clinical data. Copy number variation (CNV) data were obtained on 95 melanocytic tumors (6 ordinary nevi, 15 atypical nevi, 34 ambiguous neoplasms, and 40 melanomas) from 92 patients. The average number of significant CNVs was 0 for nevi, 0.6 for atypical nevi (range 0-3), 2.8 for ambiguous neoplasms (range 0-17), and 18.1 for melanomas (range 0-69). Clinical follow-up data were available in 57 of 95 lesions (56 of 92 patients). Tumors from patients with adverse events demonstrated an average number of CNVs of 24.5 (range 6-69) as compared with 7.9 (range 0-35) among tumors without an associated adverse event (p ≤ 0.001). No adverse events were observed in nevi including atypical nevi. Adverse events were found in 2 of 19 ambiguous neoplasms and 10 of 32 melanomas with follow up. In these two latter groups of neoplasms, the correlation between adverse events and the average number of CNVs remained statistically significant even when controlled for Breslow depth (21.5 versus 8.7, p value = 0.036). No neoplasm with adverse events had ≤3 CNVs. These results provide further evidence that SNP array testing for CNVs may be helpful in the classification and prognostication of ambiguous neoplasms. Based on these results, an algorithmic approach to challenging melanocytic neoplasms using CNV data is suggested, using as cutoff of >3 CNVs with some caveats, as the threshold for a positive result. Future clinical validation, using a larger cohort of relevant tumors, will be necessary.


Assuntos
Biomarcadores Tumorais/genética , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
11.
Histopathology ; 74(3): 504-513, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30239030

RESUMO

AIM: Primary cutaneous neuroendocrine carcinoma, or Merkel cell carcinoma (MCC), cannot be distinguished morphologically from small-cell neuroendocrine carcinomas (SmCC) from other sites. Immunohistochemistry is required to confirm cutaneous origin, and is also used for detection of sentinel lymph node (SLN) metastases of MCC. Cytokeratin 20 (CK20) expression is commonly used for these purposes, but is negative in some MCC cases, and has unclear specificity. We evaluated immunohistochemistry for neurofilament and CK20 in MCC compared with SmCC from other sites. METHODS AND RESULTS: We evaluated neurofilament expression in 55 MCC specimens from 39 unique patients, including nine CK20-negative MCC tumours. Neurofilament expression was observed in 42 of 55 (76.4%) MCC cases, including seven of nine (77.8%) CK20-negative MCC cases. Neurofilament was expressed in nine of 12 (75%) Merkel cell polyomavirus-positive tumours and five of 10 (50%) virus-negative tumours. Compared to a standard immunohistochemical panel (cytokeratin cocktail and CK20), neurofilament was 87.5% sensitive for detecting SLN metastases. Neurofilament and CK20 expression was also assessed in 61 extracutaneous SmCC from 60 unique patients, with primary sites including lung (27), bladder (18), cervix (3), gastrointestinal tract (3), sinonasal tract (2) and other sites (7). The specificity of neurofilament and CK20 for MCC versus non-cutaneous SmCC was 96.7% and 59.0%, respectively. CONCLUSIONS: Neurofilament has superior specificity to CK20 in distinguishing MCC from non-cutaneous SmCC. Neurofilament is frequently expressed in CK20- and virus-negative MCC tumours. Limitations of neurofilament immunohistochemistry include lower sensitivity than CK20 and subtle staining in some tumours. However, our findings indicate that neurofilament is useful for excluding non-cutaneous SmCC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Célula de Merkel/diagnóstico , Filamentos Intermediários , Neoplasias Cutâneas/diagnóstico , Humanos , Imuno-Histoquímica , Queratina-20/análise , Sensibilidade e Especificidade
12.
J Am Acad Dermatol ; 80(1): 189-207.e11, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29689323

RESUMO

BACKGROUND: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy, and physician decision-making. OBJECTIVES: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology. METHODS: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience, and expert judgment, was used to develop AUC in dermatopathology. RESULTS: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate" and 52 (25%) "rarely appropriate" and 43 (20%) having "uncertain appropriateness." LIMITATIONS: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost. CONCLUSIONS: The ultimate decision to order specific tests rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-the AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.


Assuntos
Uso Excessivo dos Serviços de Saúde/prevenção & controle , Dermatopatias/patologia , Dermatologia/normas , Humanos , Patologia Clínica/normas
13.
J Cutan Pathol ; 46(7): 484-489, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30895633

RESUMO

BACKGROUND: Muir-Torre syndrome (MTS) is a rare inherited syndrome, with an increased risk of sebaceous and visceral malignancy. Prior reports suggest screening for mismatch repair (MMR) deficiency may be warranted in patients <50 years and when sebaceous neoplasms are located on a non-head and neck location. Previously, appropriate use criteria (AUC) were developed for clinical scenarios in patients >60 years concerning the use of MMR protein immunohistochemistry (MMRP-IHC). This analysis explores the appropriateness of testing in patients ≤60 years. METHODS: Panel raters from the AUC Task Force rated the use of MMRP-IHC testing for MTS for previously rated scenarios with the only difference being age. RESULTS: Results verify the previously developed AUC for the use of MMRP-IHC in neoplasms associated with MTS in patients >60 years. Results also show that in patients ≤60 years with a single sebaceous tumor on a non-head and neck site, MMRP-IHC testing should be considered. Testing can also be considered with a 2-antibody panel on periocular sebaceous carcinoma in younger patients. CONCLUSIONS: Our findings align with known evidence supporting the need to incorporate clinical parameters in identifying patients at risk for MTS, with age being a factor when considering MMRP-IHC testing.


Assuntos
Envelhecimento , Síndrome de Muir-Torre , Idoso , Envelhecimento/metabolismo , Envelhecimento/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Síndrome de Muir-Torre/diagnóstico , Síndrome de Muir-Torre/metabolismo , Síndrome de Muir-Torre/patologia
15.
J Cutan Pathol ; 45(8): 563-580, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29566273

RESUMO

BACKGROUND: Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision-making. OBJECTIVES: The American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology. METHODS: The RAND/UCLA appropriateness methodology, which combines evidence-based medicine, clinical experience and expert judgment, was used to develop AUC in dermatopathology. RESULTS: With the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered "usually appropriate," 52 (25%) "rarely appropriate" and 43 (20%) "uncertain appropriateness." LIMITATIONS: The methodology requires a focus on appropriateness without comparison between tests and irrespective of cost. CONCLUSIONS: The ultimate decision of when to order specific test rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness-AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed "uncertain appropriateness" and where consensus was not reached may benefit from further research.


Assuntos
Dermatologia , Medicina Baseada em Evidências , Patologia , Testes Diagnósticos de Rotina , Humanos , Estados Unidos
16.
Gynecol Oncol ; 147(2): 351-357, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28844540

RESUMO

OBJECTIVE: Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS. METHODS: A large retrospective cohort of patients with MOGS (n=59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF, KIT, NRAS, and CTNNB1. RESULTS: Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched. CONCLUSIONS: Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS.


Assuntos
Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/patologia , Melanoma/genética , Melanoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Adulto Jovem , beta Catenina/genética
17.
J Surg Oncol ; 116(8): 1185-1192, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28715140

RESUMO

BACKGROUND AND OBJECTIVES: Current literature may overestimate the risk of nodal metastasis from thin melanoma due to reporting of data only from lesions treated with SLNB. Our objective was to define the natural history of thin melanoma, assessing the likelihood of nodal disease, in order to guide selection for SLNB. METHODS: Retrospective review. The primary outcome was the rate of nodal disease. Clinicopathologic factors were evaluated to find associations with nodal disease. RESULTS: Five hundred and twelve lesions, follow up available for 488 (median: 48 months). Lesions treated with WLE/SLNB compared to WLE alone were more likely to have high-risk features. The rate of nodal disease was higher in the WLE/SLNB group (24 positive SLNB, five false-negative SLNB with nodal recurrence: 10.2%) compared to WLE alone (four nodal recurrences: 2.0%). Univariate analysis showed age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm2 , and ulceration were associated with nodal disease. Multivariate analysis confirmed the association of age ≤45 and ulceration. CONCLUSIONS: SLNB for melanoma 0.75-0.99 mm should be considered in patients age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm2 , and/or with ulceration. Thin melanoma <0.85 mm without high-risk features may be treated with WLE alone.


Assuntos
Melanoma/patologia , Biópsia de Linfonodo Sentinela , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Excisão de Linfonodo , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Adv Anat Pathol ; 23(1): 24-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26645459

RESUMO

The following communication summarizes the proceedings of a 1-day Workshop of the International Melanoma Pathology Study Group, which was devoted to thin melanoma. The definitions and histologic criteria for thin melanoma were reviewed. The principal differential diagnostic problems mentioned included the distinction of thin melanoma from nevi, especially from nevi of special site, irritated nevi, inflamed and regressing nevi, and dysplastic nevi. Histologic criteria for this analysis were discussed and the importance of clinico-pathologic correlation, especially in acral sites, was emphasized. Criteria for the minimal definition of invasion were also discussed. In addition, a new technique of m-RNA expression profiling with 14 genes was presented and facilitated the distinction of thin melanomas from nevus in histologically obvious cases. However, for particular nevi, it was not obvious why the results indicated a malignant lesion. Despite many molecular and other ancillary investigations, Breslow thickness remains the most important prognostic factor in thin melanoma. The prognostic significance of radial (horizontal) and vertical growth phases, Clark level, regression, and mitotic rate were also discussed. Because of the increasing frequency of thin melanomas, there is a great need to develop more refined predictors of thin melanomas with worse clinical outcome.


Assuntos
Melanoma/patologia , Neoplasias Cutâneas/patologia , Humanos
19.
J Am Acad Dermatol ; 75(2): 356-63, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27189823

RESUMO

BACKGROUND: Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. OBJECTIVE: We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. METHODS: Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. RESULTS: Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. LIMITATIONS: This was a small sample size of experienced pathologists in a testing situation. CONCLUSION: Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care.


Assuntos
Melanócitos/patologia , Melanoma/classificação , Melanoma/patologia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/patologia , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnóstico , Terminologia como Assunto
20.
Cancer Cell ; 13(2): 117-28, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18242512

RESUMO

Recent evidence suggests that alterations in the self-renewal program of stem/progenitor cells can cause tumorigenesis. By utilizing genetically engineered mouse models of neurofibromatosis type 1 (NF1), we demonstrated that plexiform neurofibroma, the only benign peripheral nerve sheath tumor with potential for malignant transformation, results from Nf1 deficiency in fetal stem/progenitor cells of peripheral nerves. Surprisingly, this did not cause hyperproliferation or tumorigenesis in early postnatal period. Instead, peripheral nerve development appeared largely normal in the absence of Nf1 except for abnormal Remak bundles, the nonmyelinated axon-Schwann cell unit, identified in postnatal mutant nerves. Subsequent degeneration of abnormal Remak bundles was accompanied by initial expansion of nonmyelinating Schwann cells. We suggest abnormally differentiated Remak bundles as a cell of origin for plexiform neurofibroma.


Assuntos
Bainha de Mielina/patologia , Neurofibroma/patologia , Células de Schwann/patologia , Animais , Biomarcadores/metabolismo , Linhagem da Célula , Proliferação de Células , Progressão da Doença , Feto/citologia , Feto/metabolismo , Marcação de Genes , Proteína Glial Fibrilar Ácida/metabolismo , Integrases/metabolismo , Camundongos , Mutação/genética , Neurofibromina 1/metabolismo , Receptor de Fator de Crescimento Neural/metabolismo , Recombinação Genética , Nervo Isquiático/embriologia , Nervo Isquiático/patologia , Nervo Isquiático/ultraestrutura , Células-Tronco/citologia , Células-Tronco/metabolismo
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