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2.
Artigo em Inglês | MEDLINE | ID: mdl-32516521

RESUMO

This review discusses the definition and major categories of cutaneous T-cell lymphoma, Sézary syndrome and mycosis fungoides, and the role of immunophenotyping in their diagnosis. The following key points are raised: (a) Sézary syndrome and mycosis fungoides cells most often have a characteristic CD3+ CD4+ CD7- and/or CD26- immunophenotype. (b) This immunophenotype is not specific, but can assist in the distinction from non-neoplastic T cells and other subtypes of mature T-cell neoplasm. (c) However, small subsets of normal and reactive T-cells can have an overlapping immunophenotype, and can be distinguished by evaluating for additional changes in antigen expression.

3.
J Am Acad Dermatol ; 83(2): 430-439, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31499157

RESUMO

BACKGROUND: The prevalence of mycosis fungoides/Sézary syndrome (MF/SS) is higher in the black population than in the white population in the United States and worse outcomes have been observed in black patients. OBJECTIVE: To describe the outcomes and to identify prognostic factors in African American and black patients with MF/SS. METHODS: Clinical features and follow-up data were analyzed in 157 self-identified African American or black patients seen during 1994-2018. RESULTS: We included 122 patients with early stage MF and 35 patients with advanced-stage disease (median follow-up of 25 months). Overall, >80% of the patients who died from disease or progressed had erythema or hyperpigmentation without hypopigmentation. Patients with hypopigmentation, either as the sole manifestation or in combination with other lesions, had better overall survival (P = .002) and progression-free survival (P = .014). Clinical stage, TNMB classification, plaque disease, and elevated serum lactate dehydrogenase were also significantly associated with outcomes. Demographic and socioeconomic parameters were not associated with prognosis. LIMITATIONS: A retrospective study at a single cancer center. CONCLUSION: MF/SS manifestations and outcomes in African American and black patients are heterogeneous. Demographic and socioeconomic factors do not seem to have a prognostic role, while clinical characteristics might help in the stratification of risk of progression and shorter survival, allowing for individually tailored therapeutic interventions.

4.
Am J Dermatopathol ; 41(11): e139-e143, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31169525

RESUMO

Mycosis fungoides (MF) variants with different clinicopathologic and immunohistochemical features have been well-delineated. We report a case of scleromyxedematous changes arising in a patient with long-standing MF who progressed to Sézary syndrome (SS) shortly afterward. Total-skin electron-beam radiation therapy resulted in an excellent response, controlling both the MF/SS and the scleromyxedematous lesions; however, the patient died few months later. Although mucin deposition has been described in association with MF/SS (mainly follicular mucinosis in folliculotropic MF), there are limited reports in the literature on dermal mucinosis and scleromyxedematous changes in MF/SS. The mechanism of this association and its prognostic implications requires further investigation.


Assuntos
Micose Fungoide/patologia , Neoplasias Primárias Múltiplas/patologia , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Idoso , Humanos , Masculino
6.
Appl Immunohistochem Mol Morphol ; 27(8): 581-583, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-29517505

RESUMO

T lymphocytes can be distinguished based on the composition of the T-cell receptor (TCR) chain in α/ß T cells and γ/δ T cells. Correspondingly, α/ß lymphomas can be distinguished from γ/δ lymphomas. The latter are rare neoplasms, which are usually confined to particular organs and tissues and carry a dismal prognosis. Until recently, monoclonal antibody (mAb) clone g3.20 to the TCR γ-chain was the reagent of choice for the immunohistochemical detection of γ/δ T cells and lymphomas in standard formalin-fixed paraffin-embedded tissues. However, due to technical problems, mAb g3.20 became recently unavailable. Our attempts to identify another commercially available clone to the TCR γ-chain were unsuccessful. However, we were able to identify a mAb (clone H-41, SC-100289; Santa Cruz, Dallas, TX) to the TCR δ-chain. H-41 works well in immunohistochemistry on paraffin-embedded tissue and comparison with previously stained cases, shows superior immunolabeling to mAb g3.20. H-41 to the TCR δ-chain appears to be a suitable reagent for the replacement of mAb g3.20.


Assuntos
Anticorpos Monoclonais/imunologia , Linfoma/diagnóstico , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/imunologia , Formaldeído , Humanos , Imuno-Histoquímica , Linfoma/imunologia , Inclusão em Parafina
7.
J Am Acad Dermatol ; 78(3): 530-539, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29132694

RESUMO

BACKGROUND: Immunodeficiency (ID) correlates with worse outcomes and decreased immune checkpoint molecule expression in melanoma. The impact of ID in mycosis fungoides (MF) is unknown. OBJECTIVE: Our goal was to evaluate the impact of ID in MF. METHODS: We conducted a case-control study of 17 patients with MF and ID versus age-, stage-, and race-matched controls as a subset of a comparative analysis of 23 patients with MF with ID (prior lymphoma, recent/current pregnancy, HIV, hypogammaglobulinemia, and prior chemotherapy) versus without ID. Programmed cell death 1 (PD1), programmed death ligand 1 (PDL1), forkhead box p3, and interleukin 17 immunohistochemistry was performed on 12 patients with ID and 10 controls. RESULTS: Patients with ID had more treatment failure (14 of 23 vs 5 of 17 [P = .028]), more treatment failure within 3 years of diagnosis (12 of 23 vs 4 of 17 [P = .050]), more angiocentrism (6 of 12 vs 0 of 10 [P = .005]), larger cells (1.92 ± 0.51 out of 3 vs 1.30 ± 0.48 out of 3 [P = .009]), more cases with at least 10% PD1 positivity (9 of 11 vs 4 of 10 [P = .031]) and at least 10% PDL1 positivity (7 of 12 vs 2 of 10 [P = .042]), and a higher average percentage of PD1+ cells (43.27 ± 40.22 vs 11.2 ± 13.62 [P = .028]). No differences in survival, forkhead box p3 expression, interleukin 17 expression, histologic depth, ulceration, granulomatous changes, or syringotropism were seen. LIMITATIONS: This was a small single-center study with heterogeneous immunodeficiencies. CONCLUSION: ID correlated with worse outcomes and increased PD1 and PDL1 expression in MF. Patients with MF and ID may be candidates for immune checkpoint inhibitor therapy, pending further investigation.


Assuntos
Antígeno B7-H1/metabolismo , Síndromes de Imunodeficiência/complicações , Micose Fungoide/complicações , Micose Fungoide/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Síndromes de Imunodeficiência/imunologia , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Resultado do Tratamento , Adulto Jovem
8.
Dermatol Pract Concept ; 7(4): 13-16, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29214103

RESUMO

The majority of oral pigmentations are benign lesions such as nevi, melanotic macules, melanoacanthomas or amalgam tattoos. Conversely, mucosal melanomas are rare but often lethal; therefore, excluding oral melanomas in this setting is crucial. Reflectance confocal microscopy is a non-invasive, in vivo imaging system with cellular resolution that has been used to distinguish benign from malignant pigmented lesions in the skin, and more recently in the mucosa. However, lesions located posteriorly in the oral cavity are difficult to assess visually and difficult to biopsy due to their location. Herein we present a patient with previous multiple melanomas presenting with an oral amalgam tattoo in the buccal mucosa, which was imaged using an intraoral telescopic probe attached to a commercially available handheld RCM. In this case report we describe this novel probe, the first RCM description of an amalgam tattoo and we discuss its differences with the findings described in oral melanomas.

9.
JAMA Dermatol ; 153(7): 689-693, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28492924

RESUMO

Importance: Extramammary Paget disease (EMPD) is commonly refractory to surgical and nonsurgical therapies. Identifying recurrent or persistent EMPD is challenging because the disease is multifocal, and multiple blind scouting biopsies are usually performed in this setting. Handheld reflectance confocal microscopy (HRCM) has been used to diagnose and map primary EMPD and therefore may be used to identify EMPD recurrences. Objective: To evaluate HRCM's diagnostic accuracy in the setting of recurrent or persistent EMPD as well as its potential diagnostic pitfalls. Design, Setting, and Participants: This prospective case series study included patients referred to the Dermatology Service at Memorial Sloan Kettering Cancer Center between January 1, 2014, and December 31, 2016, with biopsy-proven EMPD in whom HRCM was used to monitor treatment response. Five patients were included, and 22 sites clinically concerning for recurrent or persistent disease were evaluated using HRCM and histopathologic examination. In 2 patients, video mosaics were created to evaluate large areas. Main Outcomes and Measures: Sensitivity and specificity of HRCM in identifying recurrent or persistent EMPD; causes for false-negative results according to their location, histopathologic findings, and previous treatments. Results: Of the 22 clinically suspicious sites evaluated in 5 patients (4 men, 1 woman; median [range] age, 70 [56-77] years), 9 (40.9%) were positive for recurrent disease on HRCM and histopathologically confirmed, and 13 (59.1%) sites were negative on HRCM, but 3 of the 13 were positive for EMPD on histopathological examination. In general, HRCM had a sensitivity of 75% and a specificity of 100% in identifying recurrent or persistent EMPD. False-negative results were found in 2 patients and occurred at the margins of EMPD, close to previous biopsy sites. Creating video mosaics (or video mosaicking) seemed to improve the detection of EMPD. Conclusions and Relevance: Handheld reflectance confocal microscopy is a useful auxiliary tool for diagnosing EMPD recurrences and can be used to guide scouting biopsies, thus reducing the number of biopsies needed to render a correct diagnosis.


Assuntos
Microscopia Confocal/métodos , Recidiva Local de Neoplasia/diagnóstico , Doença de Paget Extramamária/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Biópsia/métodos , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Doença de Paget Extramamária/patologia , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Gravação em Vídeo/métodos
10.
Cornea ; 36(6): 747-748, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28399037

RESUMO

PURPOSE: To present a novel case of ocular argyrosis mimicking conjunctival melanoma. METHODS: A 48-year-old man who is a jewelry manufacturer presented with raised pigmented lesions in the inferior fornices of both eyes. Brown-black colored, follicle-like, masses were observed in both fornices. RESULTS: An incisional biopsy confirmed the presence of silver and the diagnosis of ocular argyrosis. CONCLUSIONS: Despite its limited negative health effects, ocular argyrosis should be considered in the differential diagnosis of conjunctival pigmented lesions because of the potential for misidentification of neoplastic growth.


Assuntos
Argiria/diagnóstico , Neoplasias da Túnica Conjuntiva/diagnóstico , Doenças Palpebrais/diagnóstico , Melanoma/diagnóstico , Doenças Profissionais/diagnóstico , Argiria/cirurgia , Biópsia , Diagnóstico Diferencial , Doenças Palpebrais/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/cirurgia , Prata
11.
Mod Pathol ; 30(6): 877-883, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28281550

RESUMO

Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation). One central epigenetic regulator is the Polycomb repressive complex 2 (PRC2), which silences genomic regions by trimethylating (me3) lysine (K) 27 of histone H3, and thereby establishes the histone mark H3K27me3. Recent experimental research data demonstrated that PRC2 loss in mice skin results in the formation of Merkel cells. Prompted by these findings, we explored a possible contribution of PRC2 loss in human Merkel cell carcinoma. We examined the immunohistochemical expression of H3K27me3 in 35 Merkel cell carcinomas with pure histological features (22 primary and 13 metastatic lesions) and in 5 combined squamous and neuroendocrine carcinomas of the skin. We found a strong reduction of H3K27me3 staining in tumors with pure histologic features and virus-positive Merkel cell carcinomas. Combined neuroendocrine carcinomas had no or only minimal loss of H3K27me3 labeling. Our findings suggest that a PRC2-mediated epigenetic deregulation may play a role in the pathogenesis of virus-positive Merkel cell carcinomas and in tumors with pure histologic features.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Célula de Merkel/química , Histonas/análise , Poliomavírus das Células de Merkel/isolamento & purificação , Infecções por Polyomavirus/virologia , Neoplasias Cutâneas/química , Infecções Tumorais por Vírus/virologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/virologia , Metilação de DNA , Análise Mutacional de DNA , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Metilação , Pessoa de Meia-Idade , Mutação , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia
12.
Dermatol Pract Concept ; 7(1): 19-22, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28243489
13.
Mod Pathol ; 30(5): 761-772, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28128277

RESUMO

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αß T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αß/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.


Assuntos
Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Linfócitos T Citotóxicos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Organização Mundial da Saúde , Adulto Jovem
14.
Am J Dermatopathol ; 39(2): 155-156, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28134735
16.
Mod Pathol ; 29(2): 122-30, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26541273

RESUMO

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.


Assuntos
Carcinoma de Célula de Merkel/secundário , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Célula de Merkel/terapia , Distribuição de Qui-Quadrado , Feminino , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Fatores de Tempo , Resultado do Tratamento
17.
Dermatol Online J ; 21(7)2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26436979

RESUMO

Small bowel adenocarcinoma (SBA) is a rare primary gastrointestinal malignancy. We present a 60-year old man who developed a cutaneous metastasis of jejunal adenocarcinoma to his neck. This case highlights the clinicopathologic and immunophenotypic features of this uncommon cutaneous metastasis.


Assuntos
Adenocarcinoma/secundário , Neoplasias do Jejuno/patologia , Cuidados Paliativos/métodos , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/terapia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Biópsia por Agulha , Terapia Combinada/métodos , Progressão da Doença , Cuidados Paliativos na Terminalidade da Vida , Humanos , Imuno-Histoquímica , Neoplasias do Jejuno/terapia , Masculino , Pessoa de Meia-Idade , Pescoço , Doenças Raras , Neoplasias Cutâneas/patologia
18.
J Am Acad Dermatol ; 73(6): 968-75, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26433246

RESUMO

BACKGROUND: Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma, associated with Merkel cell polyomavirus. MCC admixed with squamous cell carcinoma (SCC) is unassociated with polyomavirus, and is genetically distinct. OBJECTIVE: We sought to distinguish clinically and dermoscopically between MCC and SCC/MCC. METHODS: We compared patient data for SCC/MCC (n = 26) and MCC (n = 20), and reviewed clinical and dermoscopic images (n = 9) of SCC/MCC. RESULTS: Patients with SCC/MCC were older (median 76.5 vs 69 years) and more often male (77% vs 60%), and had more nonmelanoma skin cancer (85% vs 25%), malignant extracutaneous tumors (25% vs 5%), lymphoproliferative disorders (23% vs 10%), and immunodeficient/proinflammatory states (77% vs 35%). In all, 58% of SCC/MCC versus 10% of MCC were clinically diagnosed nonmelanoma skin cancer. Patients with SCC/MCC had more metastases (77% vs 40%), more treatment failures (53% vs 45%), shorter survival (41 vs 54 months), and more death from disease (50% vs 40%). SCC/MCC demonstrated marked scale (7/9), and telangiectasia (1/9). Dermoscopically, small dotted and short linear irregular peripheral vessels and central milky-red areas with large-diameter arborizing vessels were seen. LIMITATIONS: The rarity of SCC/MCC limits available data. CONCLUSIONS: SCC/MCC is aggressive, arising within elderly patients' chronically ultraviolet-exposed skin, often in the setting of immunosuppression or inflammation. Dermoscopically, polymorphous vessels in lesions suspicious for nonmelanoma skin cancer are suggestive.


Assuntos
Carcinoma de Célula de Merkel/patologia , Carcinoma de Células Escamosas/patologia , Dermoscopia/métodos , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/mortalidade , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/mortalidade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
19.
Am J Dermatopathol ; 37(7): 523-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26091510

RESUMO

T-cell-depleted (TCD) allogeneic hematopoietic stem cell transplantation demonstrates similar efficacy and reduced incidence and severity of graft-versus-host disease (GVHD) in appropriately selected patients versus T-cell-replete transplantation. The histopathology of cutaneous acute GVHD (aGVHD) after TCD peripheral blood stem cell transplants (PBSCTs) is not described. We identified 13 cases of patients after TCD PBSCT, with definitive aGVHD, and 20 cases of non-aGVHD skin rash in patients after TCD PBSCT, during multidisciplinary review by a dermatopathologist, dermatologist, and transplant physician, incorporating clinical presentation, therapeutic response, and histopathology data. Histopathologic features of aGVHD and non-aGVHD skin rash in TCD PBSCT patients were compared to each other, and also to features recently reported for non-TCD transplant recipients. aGVHD and non-aGVHD skin rash in TCD PBSCT patients' biopsies had similar rates of epidermal acanthosis, dermal melanophages, neutrophils, plasma cells, eosinophils, and extravasated erythrocytes. While satellitosis, exocytosis and adnexal involvement slightly favored aGVHD, more notable differential findings favoring aGVHD were diffuse (vs. focal/absent) basal vacuolization (77% aGVHD vs. 25% non-aGVHD rash), involvement of the entire epidermis (vs. partial thickness) by necrotic keratinocytes (42% aGVHD vs. 0% non-aGVHD rash), and nondense (rather than exuberant) inflammatory infiltrates (77% vs. 20%). After filtering features seen in all TCD samples (epidermal acanthosis, dermal melanophages, neutrophils, plasma cells, eosinophils, and extravasated erythrocytes), the most distinct features belonging to aGVHD-positive TCD samples were diffuse basal vacuolization, slight rather than dense inflammatory infiltrates, and necrotic keratinocytes involving the entire epidermis. Awareness of these features may help when evaluating a skin rash occurring after a TCD transplant.


Assuntos
Exantema/patologia , Doença Enxerto-Hospedeiro/patologia , Queratinócitos/patologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Doença Aguda , Adulto , Idoso , Dermatite/etiologia , Dermatite/patologia , Diagnóstico Diferencial , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Necrose/patologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Linfócitos T
20.
Mod Pathol ; 28(8): 1023-32, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26022453

RESUMO

Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven 'pure' Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52-89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.


Assuntos
Biomarcadores Tumorais , Carcinoma de Célula de Merkel/química , Carcinoma de Célula de Merkel/genética , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/genética , Imuno-Histoquímica , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/genética , Neoplasias Cutâneas/química , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma de Célula de Merkel/etnologia , Carcinoma de Célula de Merkel/patologia , Carcinoma de Células Escamosas/etnologia , Carcinoma de Células Escamosas/patologia , Análise Mutacional de DNA , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Queratina-20/análise , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Complexas Mistas/etnologia , Neoplasias Complexas Mistas/patologia , Proteínas de Neurofilamentos/análise , Fenótipo , Valor Preditivo dos Testes , Proteína do Retinoblastoma/análise , Proteína do Retinoblastoma/genética , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Fatores de Transcrição/análise , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genética , Proteínas Supressoras de Tumor/análise
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