RESUMO
PURPOSE: The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit. METHODS: Immunohistochemical staining for the programmed death-1 receptor and ligand was performed on exenteration specimens of invasive cutaneous orbital malignancies (n = 12) and nodular basal cell carcinoma (n = 10). The numbers of positively-staining cells/40× field were counted across 5 consecutive fields, and statistical analyses were performed to compare the differences between the 2 groups. RESULTS: Programmed death-1 receptor positivity was seen in means of 30.9 cells/40× field and 62.4 cells/40× field for nodular basal cell carcinomas and invasive malignancies, respectively (p = 0.0046). A mean of 4.54 cells/40× field stained positively for the programmed death-1 ligand in nodular basal cell carcinoma, whereas a mean of 46.4 cells/40× field stained positively for programmed cell death ligand-1 in orbital invasive cutaneous carcinomas (p = 0.0015). Both of these differences were statistically significant. CONCLUSIONS: Both the programmed death-1 receptor and its ligand are enriched in invasive cutaneous malignancies. This finding indicates that negative regulation of the immune system likely prohibits tumor surveillance, and facilitates increasing aggressiveness and invasion of cutaneous malignancies.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Basocelular/imunologia , Neoplasias Orbitárias/imunologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Cutâneas/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The expression of TRPM1 (melastatin) mRNA is an independent marker, as measured by radioactive in situ hybridization (RISH), of disease-free survival in primary cutaneous melanoma (PM). The aim of the study was to determine if chromogenic in situ hybridization (CISH) can reproduce results examining diagnostic and prognostic utility of TRPM1 mRNA expression in melanocytic proliferations as measured by RISH. METHODS: The expression of TRPM1 mRNA was detected by CISH in melanocytic nevi (MN, n = 61), PM (n = 145) and metastatic melanomas (MMs, n = 15). RESULTS: A progressive loss of TRPM1 was found moving from MN to PM to MM. The histologic stepwise model of melanoma progression revealed that loss of TRPM1 occurred at the transition of RGP PM to VGP PM. As a diagnostic marker, TRPM1 gradient loss showed 93.8% sensitivity and 52.4% specificity for PM. Loss of TRPM1 mRNA correlated with melanoma aggressiveness markers and was independent predictor of disease-free and overall survival. The corresponding survival curves for degree of melanoma pigmentation matched those for degree of loss of TPRM1 mRNA. CONCLUSION: Loss of TRPM1 mRNA expression appears to be a crucial event in the progression of melanoma to a more malignant, metastatic phenotype.
Assuntos
Melanoma , Proteínas de Neoplasias/biossíntese , Neoplasias Cutâneas , Canais de Cátion TRPM/biossíntese , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Melanoma/metabolismo , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de SobrevidaRESUMO
The overlap of Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) is more common than it was generally accepted. Both diseases seem to be linked by a mutation in oncogenic BRAFV600E, probably an early event which occurs in bone marrow progenitor cells. In this article are described the clinical and histological findings in 2 cases of ECD-LCH overlap syndrome bearing the BRAFV600E mutation in both ECD and LCH lesions in bone and skin. In one case, lesions of ECD and LCH were situated directly site-to-site in the same bone section leading to the assumption of a common myeloid precursor cell for these diseases. Furthermore, we focus on the histopathological diagnostic criteria of cutaneous involvement in ECD. Lesional tissue shows a dermal infiltrate of lipidized CD68, CD163, CD1a, and langerin histiocytes admixed with Touton giant cells-a xanthogranulomatous phenotype. Often, this pattern of histopathology requires correlation with patterns of systemic involvement to differentiate ECD from other xanthogranulomatous infiltrates. This endeavor is of major importance to determine early diagnosis and treatment, because ECD often shows a poor prognosis compared with its differential diagnoses. Finally, adults who suffer from LCH and develop xanthogranulomatous infiltrates should always be screened for ECD-LCH overlap syndrome.
Assuntos
Doença de Erdheim-Chester/patologia , Histiocitose de Células de Langerhans/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Dermatopatias/patologia , Idoso , Doença de Erdheim-Chester/genética , Feminino , Histiocitose de Células de Langerhans/genética , Humanos , Mutação , Dermatopatias/genéticaRESUMO
BACKGROUND: Giant basal cell carcinomas (GBCCs), (BCC ≥ 5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect. OBJECTIVES: To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD). METHODS: Case-control study examining clinicopathologic and neuroactive factors (ß-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors. RESULTS: Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more ß-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000). CONCLUSIONS: GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuromediators deserves further study.
Assuntos
Carcinoma Basocelular/patologia , Serotonina/biossíntese , Neoplasias Cutâneas/patologia , beta-Endorfina/biossíntese , Hormônio Adrenocorticotrópico/análise , Hormônio Adrenocorticotrópico/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/psicologia , Estudos de Casos e Controles , Encefalina Metionina/análise , Encefalina Metionina/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Serotonina/análise , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/psicologia , Adulto Jovem , beta-Endorfina/análiseRESUMO
BACKGROUND: Comprehensive genomic profiling of clinical samples by next-generation sequencing (NGS) can identify one or more therapy targets for the treatment of metastatic melanoma (MM) with a single diagnostic test. METHODS: NGS was performed on hybridization-captured, adaptor ligation-based libraries using DNA extracted from 4 formalin-fixed paraffin-embedded sections cut at 10 microns from 30 MM cases. The exons of 182 cancer-related genes were fully sequenced using the Illumina HiSeq 2000 at an average sequencing depth of 1098X and evaluated for genomic alterations (GAs) including point mutations, insertions, deletions, copy number alterations, and select gene fusions/rearrangements. Clinically relevant GAs (CRGAs) were defined as those identifying commercially available targeted therapeutics or therapies in registered clinical trials. RESULTS: The 30 American Joint Committee on Cancer Stage IV MM included 17 (57%) male and 13 (43%) female patients with a mean age of 59.5 years (range 41-83 years). All MM samples had at least 1 GA, and an average of 2.7 GA/sample (range 1-7) was identified. The mean number of GA did not differ based on age or sex; however, on average, significantly more GAs were identified in amelanotic and poorly differentiated MM. GAs were most commonly identified in BRAF (12 cases, 40%), CDKN2A (6 cases, 20%), NF1 (8 cases, 26.7%), and NRAS (6 cases, 20%). CRGAs were identified in all patients, and represented 77% of the GA (64/83) detected. The median and mean CRGAs per tumor were 2 and 2.1, respectively (range 1-7). CONCLUSION: Comprehensive genomic profiling of MM, using a single diagnostic test, uncovers an unexpectedly high number of CRGA that would not be identified by standard of care testing. Moreover, NGS has the potential to influence therapy selection and can direct patients to enter relevant clinical trials evaluating promising targeted therapies.
Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Melanoma/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biologia Computacional , Bases de Dados Genéticas , Desenho de Fármacos , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/secundário , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
Pigmented epithelioid melanocytoma (PEM) is a tumor encompassing epithelioid blue nevus of Carney complex (EBN of CNC) and was previously termed animal-type melanoma. Histologically PEMs are heavily pigmented spindled and epithelioid dermal melanocytic tumors with infiltrative borders, however, their origin remains unclear. Stem cells for the epidermis and hair follicle are located in the bulge area of the hair follicle with the potential to differentiate into multiple lineages. Multiple cutaneous carcinomas, including follicular cutaneous squamous cell carcinoma (FSCC), are thought to arise from stem cells in the follicular bulge. We present two cases of PEM/ATM in a 63 year-old male on the scalp with follicular origin and a 72 year-old female on the upper back arising in an intradermal nevus. Biopsy of both cases revealed a proliferation of heavily pigmented dermal nests of melanocytes with atypia. The Case 1 tumor was in continuation with the outer root sheath of the hair follicle in the bulge region. Case 2 arose in an intradermal melanocytic nevus. Rare mitotic figures, including atypical mitotic figures, were identified in both cases. We present two cases of PEM, with histologic evidence suggesting two origins: one from the follicular bulb and one from an intradermal nevus.
Assuntos
Neoplasias de Cabeça e Pescoço , Melanoma , Nevo Intradérmico , Neoplasias Cutâneas , Idoso , Animais , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Melanoma/metabolismo , Melanoma/patologia , Nevo Intradérmico/metabolismo , Nevo Intradérmico/patologia , Couro Cabeludo/metabolismo , Couro Cabeludo/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: The authors hypothesized that comprehensive genomic profiling of advanced-stage cutaneous squamous cell carcinoma (cSCC) could identify genomic-derived drug targets of therapy for patients with conventional therapy-resistant disease. METHODS: Comprehensive genomic profiling of 315 cancer genes was applied to 50 ng of DNA from 122 cSCC cases for the evaluation of all classes of genomic alterations (GAs). Clinically relevant genomic alterations (CRGAs) were defined as those identifying anticancer drugs on the market or in registered clinical trials. RESULTS: There were 21 women (17%) and 101 men (83%) with a median age of 64.9 years (range, 21-87 years). Eleven cSCC cases (9%) were histologic AJCC grade 1, 69 (57%) were grade 2, and 42 (34%) were grade 3. The primary cSCC was used for sequencing in 77 cases (63%). Metastatic lesions were sequenced in 37% of cases. There were 1120 total GAs identified (average of 9.2 GAs per tumor), with 100% of cases harboring at least 1 alteration. Of the 122 cSCCs, 107 (88%) harbored at least 1 CRGA (2.5 CRGAs per cSCC) includingNOTCH1 (43%); patched 1 (PTCH1) (11%); BRCA2 (10%); HRAS (8%); ataxia telangiectasia mutated (ATM) (7%); erb-B2 receptor tyrosine kinase 4 (ERBB4) (7%); neurofibromatosis type 1 (NF1) (7%); erb-B2 receptor tyrosine kinase 2 (ERBB2) (6%); phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) (6%); cyclin D1 (CCND1) (6%); epidermal growth factor receptor (EGFR) (5%); and F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) (5%). CONCLUSIONS: In the current study, approximately 88% of patients with cSCC were found to harbor clinically relevant GAs that have the potential to guide the treatment of patients with advanced-stage tumors with targeted therapeutic agents. Cancer 2016;122:249-257. © 2015 American Cancer Society.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Perfilação da Expressão Gênica/métodos , Terapia de Alvo Molecular/métodos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: Acne agminata has only been rarely reported in the ocular adnexa. This study was undertaken to identify histopathological, clinical, and management features of this disorder. METHODS: A computerized database was utilized to identify cases of ocular adnexal acne agminata. Via chart review and light microscopy, clinical and histopathologic aspects of this dermatosis were collected, and statistical analyses were performed. RESULTS: Twelve cases (5 males, 7 females, mean age = 50.5 years) of clinically and histopathologically confirmed ocular adnexal acne agminata were identified. The main variant of granuloma was sarcoidal in 6 cases (50%) and tuberculoid in 5 cases (41.7%), although 9 specimens (75%) displayed greater than 1 variant of granuloma. In addition, specimens demonstrated varying degrees of fibrosis (8 cases, 66.7%), necrosis (6 cases, 50%), spongiosis (5 cases, 41.7%), and perifollicular inflammation (6 cases, 50%). All specimens showed signs of lymphstasis-lymphangiectasis. At a minimum of 6-month postprocedure interval, all patients experienced complete relief of their symptoms and did not experience recurrence. CONCLUSIONS: This study represents the largest cohort of ocular adnexal acne agminata, and revealed a spectrum of granulomatous subtypes, including coexistence of different granuloma subtypes within the same specimen. Lymphangiectases is a hallmark of this disorder, and varying features of tissue reaction are typical features of acne agminata. All of these cases were successfully cured by surgical resection of lesions without recurrence at last follow-up, and this modality should be considered the standard of care in the management of this problem.
Assuntos
Erupções Acneiformes/patologia , Doenças Palpebrais/patologia , Lúpus Eritematoso Cutâneo/patologia , Dermatopatias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Feminino , Humanos , Linfangiectasia/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.
Assuntos
Carcinoma Intraductal não Infiltrante/patologia , Carcinoma de Células Escamosas/patologia , Glândulas Exócrinas/patologia , Vulva/patologia , Neoplasias Vulvares/patologia , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Carcinossarcoma/patologia , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Glândulas Mamárias Humanas , Metástase Neoplásica/radioterapia , Recidiva Local de Neoplasia/cirurgia , Doença de Paget Extramamária/patologia , Líquen Escleroso Vulvar/complicações , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/cirurgiaRESUMO
The Jarisch-Herxheimer reaction (JHR) is a transient inflammatory syndrome triggered hours after the start of antibiotic treatment of spirochete infections, namely syphilis. Clinically, JHR manifests as an abrupt onset of constitutional symptoms and exacerbation of cutaneous lesions that resolve without intervention. JHR's pathogenesis is unclear and it is histopathologically rarely reported. Herein, the authors report a 47-year-old woman, with solitary erythema migrans and positive Lyme disease serology, who presented for medical care 14 days after commencement of doxycycline therapy. She complained of malaise, facial flushing, gingival erythema, and acquisition of additional plaques characterized by swelling, increased erythema, pruritus, and exfoliative scale. Punch biopsies demonstrated subacute to chronic spongiotic psoriasiform reaction patterns with a superficial lymphocytic infiltrate. By Borrelia-specific immunohistochemistry, spirochetes were found in the deep dermis, unassociated with inflammation, and focally in the upper spinous layer, associated with spongiosis. Borrelia burgdorferi DNA was detected by nested polymerase chain reaction. Doxycycline was discontinued, and symptoms and signs resolved within a few days. Liberation of endotoxin-like materials (eg, lipoproteins) from degenerating spirochetes and concomitant cytokine production is the suspected cause of JHR and supported by the finding of lesional spirochetes. Alternatively, a reversal reaction with a delayed-type hypersensitivity reaction is also a plausible cause based on spirochetes found in the lymphocytic spongiotic dermatitis.
Assuntos
Antibacterianos/efeitos adversos , Doxiciclina/efeitos adversos , Toxidermias/etiologia , Toxidermias/patologia , Eritema Migrans Crônico/tratamento farmacológico , Eritema Migrans Crônico/complicações , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Onycholysis, separation of the nail plate from the nail bed, is etiologically classified as primary (idiopathic) or secondary (eg, caused by psoriasis, squamous cell carcinoma). Repetitive microtrauma plays a role in idiopathic onycholysis and also facilitates human papillomavirus (HPV) infection. Herein, we report a case of persistent primary onycholysis associated with repetitive trauma and infection by a multiplicity of Beta-papillomavirus (Beta-PV) genotypes. An otherwise healthy 27-year-old woman presented with a 6-year history of onycholysis of the halluces and right second toe. Her occupation required wearing steel-toed boots. Fungal cultures were negative and antifungal therapy was ineffective. Punch biopsy of the hallux nail bed revealed epidermal hyperplasia, acanthosis, hypergranulosis, hyperkeratosis, and regions of koilocytosis without significant inflammation. This histopathology implicated chronic irritation and HPV infection. Immunohistochemistry demonstrated productive HPV infection. Nested PCR using degenerate consensus primers revealed infection with 5 known and 1 novel Beta-PV genotypes (HPV 5, HPV 8, HPV 20, HPV 23, HPV 37, and FA25). The histopathology of primary onycholysis is unknown. Based on the aforementioned, we propose that repetitive microtrauma caused by wearing steel-toed boots promoted onycholysis and HPV infection, the latter of which, altered the differentiation of nail bed epithelium, preventing adhesion of nail plate to the nail bed. Lastly, the presence of oncogenic Beta-PV genotypes (ie, HPV 5, 8, and 20) implicates a risk for subungual squamous cell carcinoma, particularly if the nail remains symptomatic and persistently irritated.
Assuntos
Betapapillomavirus/isolamento & purificação , Unhas/virologia , Onicólise/complicações , Infecções por Papillomavirus/virologia , Adulto , Betapapillomavirus/genética , Biópsia , DNA Viral/genética , Feminino , Genótipo , Testes de DNA para Papilomavírus Humano , Humanos , Imuno-Histoquímica , Unhas/lesões , Unhas/patologia , Onicólise/diagnóstico , Onicólise/etiologia , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Previous classifications of vasculitides suffer from several defects. First, classifications may follow different principles including clinicopathologic findings, etiology, pathogenesis, prognosis, or therapeutic options. Second, authors fail to distinguish between vasculitis and coagulopathy. Third, vasculitides are systemic diseases. Organ-specific variations make morphologic findings difficult to compare. Fourth, subtle changes are recognized in the skin, but may be asymptomatic in other organs. Our aim was to use the skin and subcutis as a model and the clinicopathologic correlation as the basic process for classification. METHODS AND RESULTS: We use an algorithmic approach with pattern analysis, which allows for consistent reporting of microscopic findings. We first differentiate between small and medium vessel vasculitis. In the second step, we differentiate the subtypes of small (capillaries versus postcapillary venules) and medium-sized (arterioles/arteries versus veins) vessels. In the final step, we differentiate, according to the predominant cell type, into leukocytoclastic and/or granulomatous vasculitis. CONCLUSIONS: Starting from leukocytoclastic vasculitis as a central reaction pattern of cutaneous small/medium vessel vasculitides, its relations or variations may be arranged around it like spokes of a wheel around the hub. This may help establish some basic order in this rather complex realm of cutaneous vasculitides, leading to a better understanding in a complicated field.
Assuntos
Algoritmos , Dermoscopia/métodos , Interpretação de Imagem Assistida por Computador/métodos , Microscopia/métodos , Reconhecimento Automatizado de Padrão/métodos , Vasculite Leucocitoclástica Cutânea/patologia , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Pigmented lesions in the anogenital area encompass a wide variety of disorders including squamous intraepithelial neoplasia. The authors sought to explore the mechanism(s) underlying clinically pigmented squamous intraepithelial neoplasia in the anogenital area. A light-microscopic and immunohistochemical study of 64 lesional specimens from 45 patients (32 women, 13 men; age range, 23-73 years) with pigmented lesions in the anogenital area was performed. Histopathologically, 63 (98%) specimens showed melanin incontinence into the superficial dermis beneath the dysplastic epithelium. A focal or total loss of basilar hyperpigmentation was detected in 30 (48%) and 13 (20%) of lesions, respectively. In 17 (27%) cases, absence of basal layer hyperpigmentation was accompanied by a subepithelial lichenoid infiltrate. Melanin within the upper part of dysplastic areas were seen in 63 cases (98%), whereas dendritic melanocytes colonization, mild in all but 1 specimen case, was observed in 53 (83%) cases. All cases proved to be the usual type of squamous intraepithelial neoplasia; no single case of the simplex (differentiated) variant was present. The main mechanisms of pigmented squamous intraepithelial neoplasia of the anogenital area include melanin incontinence and occurrence of melanin in dysplastic keratinocytes. Colonization of the dysplastic epithelium by dendritic melanocytes seems to contribute, but it is rarely a prominent feature.
Assuntos
Neoplasias do Ânus/patologia , Carcinoma in Situ/patologia , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/patologia , Pigmentação da Pele , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Melaninas , Melanócitos/patologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
OBJECTIVE: To describe the clinical and pathologic features of women undergoing labioplasty for labia minora hypertrophy (LH) and to determine whether localized lymphedema plays a role in its pathogenesis. MATERIALS AND METHODS: A retrospective case series of consecutive cases of labioplasties performed for LH was retrieved from a 10-year period. Clinical, histopathologic, and immunohistochemical features were evaluated. RESULTS: Thirty-four labioplasty specimens from 31 women were identified. The women had a median/mean age of 36/35 years (range = 14-62 y) and had noted the presence of LH for a median/mean period of 36/86 months (range = 5-264 mo). A minority of patients had antecedent vaginal delivery (29%) and vulvar trauma (12%) and were either overweight (20%) or obese (27%). About half complained of vulvar appearance and approximately a third each had symptoms of pain, dyspareunia, or irritation. After a median/mean follow-up time of 40/44 months, 3 patients had recurrent LH (9%). The volume of excised tissue was greater for the patients with recurrent LH, than those without (mean of 9.8 vs 5.6 mL, respectively); however, no clinicopathologic finding predicted recurrence of LH. Histopathologically, all LH specimens showed diagnostic signs of chronic lymphedema, and compared with vulvar controls, LH had a significantly greater number of lymphangiectases (mean 15/mm vs 3/mm, p = .001) and showed greater mean maximal lymphatic dilation (0.12 vs 0.04 mm, p = .004), respectively. In addition, lichenification (94%), indicating chronic irritation, and sebaceous hyperplasia (60%), perisebaceous inflammation, and Demodex folliculorum infestation (3%), a constellation of findings commonly seen in phymatous rosacea, were evident. CONCLUSIONS: Rather than an anatomic variant, LH seems to be a manifestation of chronic lymphedema, either acquired or primary with delayed onset. Because persistent lymphedema can lead to functional debilitation, recurrent skin infections, elephantiasis, and, rarely, malignancy, early excision and treatment of factors that promote lymphedema would be effective management of this rare condition.
Assuntos
Hipertrofia/etiologia , Hipertrofia/patologia , Linfedema/complicações , Linfedema/patologia , Doenças da Vulva/etiologia , Doenças da Vulva/patologia , Adolescente , Adulto , Animais , Feminino , Histocitoquímica , Humanos , Imuno-Histoquímica , Microscopia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Microvenular hemangioma (MVH) is a rare, slowly growing, benign vascular tumor that typically presents as a solitary enlarging plaque or nodule on the trunk or the extremities of young to middle-aged adults. A minority of MVH present with multiple lesions that are either gradually or suddenly acquired (eruptive MVH). Herein, we report a case of a 53-year-old woman who progressively developed numerous bilateral MVHs presenting as enlarging, blanching, erythematous to violaceous macules, patches, and plaques over the proximal thighs and axillae. Two biopsies exhibited the irregular branching venules with inconspicuous lumina lacking endothelial atypia and associated with dermal fibrosis characteristic of MVH. Immunophenotypically, the endothelium expressed Wilms Tumor 1, CD31, CD34, and erythrocyte-type glucose transporter protein (GLUT-1) GLUT-1 focally and was negative for Human herpes virus 8 and the lymphatic marker D2-40. In addition, numerous dermal spindle cells expressing CD34 and procollagen, putative fibrocytes, surrounded the thickened dermal collagen bundles and small vessels of MVH implicating a reactive/reparative (proliferative) process due to an unrecognized cutaneous injury. A review of MVH summarizing its clinicopathologic findings and its natural history is presented.
Assuntos
Hemangioma/patologia , Neoplasias Cutâneas/patologia , Pele/irrigação sanguínea , Pele/patologia , Vênulas/patologia , Adolescente , Adulto , Biomarcadores Tumorais/análise , Biópsia , Criança , Pré-Escolar , Feminino , Hemangioma/química , Hemangioma/imunologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Pele/química , Pele/imunologia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/imunologia , Vênulas/química , Vênulas/imunologia , Adulto JovemAssuntos
Dermatoses do Pé/patologia , Hiperpigmentação/patologia , Micose Fungoide/patologia , Psoríase/patologia , Neoplasias Cutâneas/patologia , Adulto , Biópsia por Agulha , Diagnóstico Diferencial , Dermatoses do Pé/fisiopatologia , Dermatoses da Mão/patologia , Dermatoses da Mão/fisiopatologia , Humanos , Hiperpigmentação/diagnóstico , Imuno-Histoquímica , Masculino , Micose Fungoide/diagnóstico , Psoríase/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
Recently, 2 putatively novel clinicopathological entities, macular arteritis (MA) and lymphocytic thrombophilic arteritis (LTA), have been described. Both exhibit an indolent chronic course and erythematous and hyperpigmented macules (MA > LTA) and papules/plaques (LTA > MA), often in a reticulated pattern on the lower limbs. Histopathologically, they show varying degrees of lymphocyte infiltration and disruption of the arterial wall, concentric luminal fibrin deposition, and in some cases, fibrointimal scarring (endarteritis obliterans). This spectrum of histology overlaps with the subacute, reparative, and healed stages reported for cutaneous polyarteritis nodosa (CPAN). Herein, we report 2 cases of cutaneous lymphocytic arteritis, 1 with persistent indolent disease and the second with acute self-limited disease. Comparing these 2 patients' findings with that reported for MA, LTA, and CPAN highlights a clinicopathologic spectrum, which exhibits increasing disease severity moving from MA to LTA to CPAN to systemic polyarteritis nodosa. Given the clinicopathologic similarities, we conclude that our cases and cases previously reported as MA or LTA likely represent an indolent form of CPAN.
Assuntos
Poliarterite Nodosa/patologia , Dermatopatias/patologia , Adulto , Feminino , Humanos , Adulto JovemRESUMO
Brooke-Spiegler syndrome (BSS) is a rare, inherited, autosomal dominant disorder characterized by development of multiple adnexal cutaneous neoplasms including spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. The syndrome of multiple familial trichoepitheliomas (MFT) is considered a phenotypic variant of BSS in which patients present with trichoepitheliomas only. We studied germline and somatic mutations of the CYLD gene by direct sequencing in patients with BSS (n = 49) and MFT (n = 18) using peripheral blood and 90 samples of frozen or formalin-fixed paraffin-embedded tumor tissue selected from 379 available histology specimens. Germline CYLD mutations were found in 51 patients (76%) from 36 families (75%). Germline CYLD mutations were found in 43 of the 49 patients with BSS (88%) but in only 8 of 18 MFT cohort (44%). Twenty-one frameshift, 15 nonsense, 3 missense, and 4 splice site mutations were found in patients with BSS, whereas 1 frameshift, 5 nonsense, and 2 splice site mutations were identified in the MFT cohort. Five novel mutations were identified including 4 frameshift mutations (c.1027dupA/p.T343NfsX7, c.2155dupA/p.M719NfsX5, c.2288_2289delTT/p.F763X, and c.2641delG/p.D881TfsX32) and 1 nonsense mutation (c.2713C>T/p. Q905X). Of the 76 tumors from 32 patients with a germline CYLD mutation, 12 were spiradenomas, 15 spiradenocylindromas, 26 cylindromas, 15 trichoepitheliomas, and 7 were other tumor types. Somatic mutations were detected in 67 specimens of these 76 tumors (88%). Of the 67 somatic mutations, 21 (31%) represented a sequence alteration and 46 (69%) showed loss of heterozygosity. In the remaining 9 cases (12%), the somatic changes remained unknown. A germline CYLD mutation was not detected in 14 tumor samples from 8 patients. In these 14 tumors, somatic mutations were identified in 6 samples (43%), all consisting of sequence alterations (1 sample showed 2 different sequence alterations). In the remaining 8 samples (53%), neither germline nor somatic mutations were found in the lesional tissue. Our study increases the catalog of known CYLD mutations in patients with BSS/MFT to 86 and documents the variability of somatic mutations that may occur in them. We confirm the absence of firm genotype-phenotype correlations and the existence of a subset of patients with BSS/MFT who lack a demonstrable germline CYLD mutation. Further studies are needed to explain the reasons for this phenomenon.
Assuntos
Mutação , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Pele/patologia , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Códon sem Sentido , Análise Mutacional de DNA , Enzima Desubiquitinante CYLD , Feminino , Mutação da Fase de Leitura , Secções Congeladas , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Inclusão em Parafina , Linhagem , Fenótipo , Adulto JovemRESUMO
PURPOSE: To delineate signals by which the vascular abnormalities inherent to ocular rosacea arise and to correlate these signals with elements of the innate immune system. METHODS: Experimental study. Immunohistochemical staining was performed for a variety of vascular markers and for toll-like receptor-4 on eyelid biopsies taken from patients with ocular rosacea and normal controls. Statistical comparisons were then performed between the 2 groups. RESULTS: Immunohistochemical staining for CD31 and integrin-ß-3 did not demonstrate any statistically significant differences between eyelids from patients with ocular rosacea and normal controls. Cutaneous biopsies from ocular rosacea patients demonstrated statistically significant enrichments of intercellular adhesion molecule-1 and CD105 among arterioles, whereas there were no statistically significant differences in the venules between normal controls and ocular rosacea patients. The correlation between the number of toll-like receptor-4-positive cells and each vascular marker was statistically significant. CONCLUSIONS: Cutaneous biopsies of the eyelid did not demonstrate an increase in the total number of blood vessels. However, the vascular abnormalities that are typical of ocular rosacea represent activated, inflamed vessels, and these phenomena may be mediated by intercellular adhesion molecule and CD105. Furthermore, the strong correlations between toll-like receptor-4 and each vascular marker suggest that the innate immune system may govern the cutaneous effects of ocular rosacea. Intercellular adhesion molecule, CD105, and toll-like receptor-4 may represent important therapeutic targets in the management of this disease.
Assuntos
Doenças Palpebrais/patologia , Pálpebras/irrigação sanguínea , Rosácea/patologia , Receptor 4 Toll-Like/metabolismo , Antígenos CD/metabolismo , Arteríolas/imunologia , Arteríolas/patologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Endoglina , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Doenças Palpebrais/imunologia , Feminino , Humanos , Imunidade Inata , Integrina beta3/análise , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Receptores de Superfície Celular/metabolismo , Rosácea/imunologia , Vênulas/imunologia , Vênulas/patologiaRESUMO
Pathologically, Whipple disease (WD) is characterized by the accumulation of myriad macrophages parasitized by Tropheryma whipplei (TW) bacilli denoted by periodic acid-Schiff (PAS) positivity. These PAS+ macrophages are typically found in the duodenum associated with lymphangiectasia. Recently, we reported the presence of PAS+ macrophages and free TW in erythema nodosum leprosum (ENL)-like lesions and normal skin in a patient with WD who suffered from the immune reconstitution inflammatory syndrome (IRIS). We extend that report by describing the clinical and pathologic findings over 5 years of follow-up. First, the IRIS gradually diminished and abated over 18-month time. Second, at no point did WD recur, and all duodenal and skin biopsies tested by polymerase chain reaction were negative for TW DNA. Third, PAS+ macrophages were identified in 26 of 27 skin biopsies (96%) and decreased along with free TW over time. Fourth, ENL-like lesions had significantly greater numbers of PAS+ macrophages than normal skin. Moreover, normal abdominal skin (region of ENL-like lesions) had greater PAS+ counts than arm skin (not a site of IRIS). Last, lymphangiectases, a histologic sign of lymphostasis, was found in all skin biopsies. Overall, these findings implicate bacillary burden as a factor in the immune tolerance to live TW in active WD and the initiation of ENL-like nodules against dead/nonreplicative TW in treated WD. In addition, poor lymphatic drainage is likely responsible for the gradual clearance of TW from the skin and the impaired delayed-type hypersensitivity reaction (absence of activated macrophages) against TW found in WD, presumptively due to reduced/absent immune cell trafficking necessary for lymphocyte-macrophage interactions and induction of adaptive immunity.