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BACKGROUND: Apocrine cystadenoma is a rare, benign adenomatous cystic neoplasm, the pathogenesis of which is not fully understood. We sought to characterize the clinical, dermatoscopic, and histopathologic features of apocrine cystadenoma and its relationship to hidrocystoma. METHODS: We retrospectively analyzed cases of apocrine cystadenoma and hidrocystoma retrieved from the dermatopathology laboratory information system. RESULTS: Of the 350 cases apocrine cystic lesions, 13 cases of apocrine cystadenomas met the inclusion criteria. The age ranged from 20 to 84 years with an average of 64 years. They were long-standing (duration 3-15 years), slow-growing, large tumors usually found on the scalp. Dermatoscopy accentuated translucent light to dark blue color and prominent vessels that were present more at the periphery. All lesions were multilocular with columnar to cuboidal lining and decapitation secretion. A large portion of the lesion consisted of a simple nonproliferative epithelial lining, identical to that observed in apocrine hidrocystomas, while the proliferative adenomatous component made up a smaller portion with two patterns: (1) tubular proliferation, which either protruded into the cystic cavity or expanded outward peripherally, or (2) papillary projections, which were multiple layers thick with fibrovascular core, sometimes accompanied by tubular proliferation. Immunohistochemical stains showed strong staining for p40 and a sparse number of cells stained for Ki-67 and p53. CONCLUSIONS: The long duration of the lesion and the large areas of simple apocrine epithelial lining suggest that apocrine cystadenomas arise from long-standing apocrine hidrocystomas. However, the retrospective nature of the study from a single institution is a limitation.
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Cistadenoma , Hidrocistoma , Neoplasias das Glândulas Sudoríparas , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hidrocistoma/patologia , Estudos Retrospectivos , Neoplasias das Glândulas Sudoríparas/patologia , Glândulas Apócrinas/patologia , Cistadenoma/química , Cistadenoma/patologia , Proliferação de CélulasRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma. The overall risk of developing DLBCL is increased in patients with other lymphomas, such as mycosis fungoides (MF). In this report, we present an 81-year-old female with early-stage MF who simultaneously progressed to tumor stage, large-cell transformed (LCT) MF and developed a primary DLBCL in a lymph node (LN). She presented with a tumor on her leg and new lymphadenopathy in her right axilla. Skin biopsy of the tumor revealed infiltration of large atypical CD3+, CD4+, and CD30+ cells, and a smaller portion of CD8+ cells in the dermis, consistent with LCT MF. Biopsy of the axillary LN revealed diffuse sheets of CD20+, BCL-2+, c-MYC+, and CD10- cells, highly suggestive of double expressor DLBCL. High-throughput sequencing revealed monoclonal T cells in the skin tumor and a monoclonal B-cell population in the LN. The above findings led to simultaneous diagnoses of LCT MF and nodal double expressor DLBCL. Our case demonstrates the importance of performing a full pathological workup in cutaneous T-cell lymphoma patients presenting with lymphadenopathy.
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In the second part of this Continuing Medical Education article on paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome (PNP/PAMS), its diagnostic criteria, investigative work-up, and management are reviewed. PNP/PAMS is a rare autoimmune blistering disorder associated with high morbidity and mortality. Recognizing PNP/PAMS's key features and its diagnostic criteria is critical in initiating appropriate work-up. Evaluating PNP/PAMS requires knowledge of its findings on histopathology, direct immunofluorescence, indirect immunofluorescence, and enzyme-linked immunosorbent assay. Lastly, treatments for PNP/PAMS are reviewed with suggestions based on case reports and expert opinions in the literature. LEARNING OBJECTIVES: After completing this learning objective, the reader will be able to identify the criteria necessary for diagnosing paraneoplastic pemphigus (PNP/PAMS), learn how to work-up a diagnosis of PNP/PAMS, and understand important principles in the management of PNP/PAMS.
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Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome (PNP/PAMS) is a highly fatal autoimmune blistering disease. The condition occurs in patients with underlying benign or malignant neoplasms, most commonly lymphoproliferative disorders. Both humoral and cell-mediated immunities contribute to the pathogenesis, and autoantibodies against plakin family proteins are characteristic. Patients typically present with severe stomatitis and polymorphous skin lesions, which are often resistant to treatment. Bronchiolitis obliterans (BO) is a frequent complication which contributes to the high mortality rate of PNP/PAMS. Given the rarity of this disorder and heterogeneity of clinical presentation, clinicians should maintain a high index of suspicion for PNP/PAMS to avoid delayed diagnosis. In this first part of a two-part continuing medical education (CME) series, risk factors, pathogenesis, and clinical features of PNP/PAMS are discussed.
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BACKGROUND: Biopsy specimens go through a diagnostic pathway before a pathology report is rendered for the clinician. Errors can occur at any step in this pathway. METHODS: A 1-year prospective study was conducted at a single academic institution to identify and characterize errors that occurred in the diagnostic pathway from the clinic to the dermatopathology lab. RESULTS: A total of 25 662 specimens were processed and 190 errors were recorded (an error rate of 0.7%). The most common errors were an incorrect biopsy site (n = 65), incorrect data entry of a correct diagnosis (n = 25), and specimen mix-up (n = 23). There were 17 diagnostic errors. Errors most often occurred in the pre-analytical phase (n = 128). The clinician was responsible for 34.2% of errors, the dermatopathologist for 23.7%, and the histotechnician for 18.9%. Slips were the most common type of human error (n = 156). CONCLUSION: The most common error involved an incorrect biopsy site at the clinical stage. Over two-thirds of errors occurred before the slide reached the dermatopathologist. Diagnostic errors (analytical phase) rarely occurred, and when they did occur, the clinician was most likely to discover the error. Examining and addressing common laboratory errors help to reduce their incidence and lead to quality improvement in dermatopathology.
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Estudos Prospectivos , Humanos , Erros de Diagnóstico , BiópsiaRESUMO
Syphilis is growing ever more prevalent in the United States with its incidence rising every year. Dermatopathologists need to maintain a high index of suspicion to avoid delayed diagnosis of this treatable disease. Accordingly, it is imperative to be aware of its myriad of presentations-including secondary syphilis with granulomatous inflammation. Most cases show aggregations of epithelioid histiocytes associated with plasma cells. Other patterns include an interstitial granuloma-annulare-like pattern, sarcoidal, and tuberculoid pattern. Immunohistochemical stains for Treponema pallidum may be negative, especially in late secondary or tertiary syphilis. We present a case of nodular secondary syphilis with granulomatous inflammation with negative T. pallidum staining.
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Granuloma Anular , Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/complicações , Treponema pallidum , Inflamação/complicaçõesRESUMO
Exogenous ochronosis refers to accumulation of homogentisic acid metabolites in tissues, manifesting as pigmentation of affected tissues. Phenolic compounds are most commonly implicated, including hydroquinone, quinine, phenol, resorcinol, mercury, and picric acid. The affected connective tissues exhibit brownish discoloration when heavily pigmented and the histopathological appearance is characteristic with "banana-shaped" ochre-colored pigment deposits. Herein, the authors describe a rare case of exogenous ochronosis involving the conjunctiva, sclera and skin, as a result of chronic use of Teavigo (94% epigallocatechin gallate), a polyphenol compound with postulated antioxidant and antiapoptotic activity.
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Alcaptonúria , Ocronose , Transtornos da Pigmentação , Humanos , Ocronose/induzido quimicamente , Ocronose/diagnóstico , Ocronose/patologia , Alcaptonúria/patologia , Pele/patologiaRESUMO
Pigmented purpuric lichenoid dermatitis (PPLD) is a rare subtype of pigmented purpuric dermatosis, which classically presents with a mixture of lichenoid papules and patches on the bilateral lower extremities. Herein, we describe an unusual case of a 47-year-old man with PPLD who presented with 1-3mm discrete papules without the presence of larger patches. The diagnosis of PPLD should be considered for patients presenting with bilateral symmetric discrete papules on the legs.
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Dermatite , Eczema , Ceratose , Transtornos da Pigmentação , Púrpura , Masculino , Humanos , Pessoa de Meia-Idade , Púrpura/diagnóstico , Púrpura/etiologia , Transtornos da Pigmentação/diagnóstico , Eczema/diagnóstico , Ceratose/diagnóstico , Diagnóstico Diferencial , Dermatite/diagnósticoRESUMO
ABSTRACT: Sarcomatoid dedifferentiated melanoma (SDDM) represents a diagnostic challenge as this cutaneous spindle cell melanoma lacks expression of classic melanocytic markers including S100, SOX10, Melan-A, HMB45, and MITF. The expression of the emerging melanoma marker preferentially expressed antigen in melanoma (PRAME) in SDDM is largely unknown. In this article, a case of SDDM arising in association with a nodular melanoma is highlighted. A 65-year-old man presented with a several week history of an ulcerated lesion on the right medial knee. A shave biopsy of the lesion revealed a biphasic neoplasm, which consisted of a centrally located poorly differentiated spindle cell component and an adjacent nodular component consisting of atypical melanocytes arranged in nests and fascicles. While the nodular component stained for S100, SOX10, and Melan-A, the spindle cell component failed to stain for these conventional melanocytic markers, only staining diffusely for CD10 and faintly for CD68. Both components stained for PRAME diffusely albeit less intensely within the spindle cell component. Next-generation DNA sequencing assay of the microdissected biphasic components revealed a shared mutation of NRAS. The results of the PRAME immunohistochemical stain and next-generation DNA sequencing assay facilitated in establishing the diagnosis of SDDM in association with nodular melanoma.
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Melanoma/diagnóstico , Neoplasias Complexas Mistas/diagnóstico , Sarcoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Terapia Combinada , Diagnóstico Diferencial , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Joelho , Masculino , Melanoma/patologia , Melanoma/terapia , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/terapia , Sarcoma/patologia , Sarcoma/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapiaRESUMO
A 58-year-old woman with a history of morbid obesity, asthma, and prior warfarin use presented to the hospital with shortness of breath and a three-month history of painful, ulcerated ulcers with retiform purpura of her bilateral distal extremities. A punch biopsy specimen demonstrated focal necrosis and hyalinization of the adipose tissue with subtle arteriolar calcium deposition, findings consistent with calciphylaxis. We discuss the presentation of non-uremic calciphylaxis and review the risk factors, pathophysiology, and interdisciplinary management approach of this rare disease.
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Calciofilaxia , Humanos , Feminino , Pessoa de Meia-Idade , Calciofilaxia/patologia , Fatores de Risco , Varfarina/efeitos adversos , Pele/patologiaRESUMO
Sarcomatoid dedifferentiated melanoma (SDDM) is a recently recognized subtype of melanoma that stains diffusely for CD10 and lacks the expression of the usual melanocytic markers including S100, SOX10, MITF, and Melan A. Advances in next-generation DNA sequencing technology have facilitated the increased recognition of this rare, aggressive spindle cell melanoma. Herein, a case of relatively early lesion of SDDM arising in association with melanoma in situ is highlighted. A 72-year-old man with a history of previously treated melanoma in situ on the face five years prior presented with a new rapidly growing lesion within the scar of the treated site. A shave biopsy of the lesion revealed a centrally located 1.8-mm deep, poorly differentiated spindle cell neoplasm in association with an adjacent recurrent melanoma in situ. The spindle cell component stained diffusely for CD10, but failed to stain for S100, SOX10, and Melan-A while the melanoma in situ expressed all three melanocytic markers. Next-generation DNA sequencing assay revealed mutations in NF1, CDKN2A, TP53, and TSC1. A diagnosis of stage 2B SDDM arising in association with melanoma in situ was established based on the clinical context and genomic assay results.
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Melanoma/patologia , Sarcoma/diagnóstico , Neoplasias Cutâneas/complicações , Neoplasias de Tecidos Moles/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia/métodos , Desdiferenciação Celular , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imuno-Histoquímica/métodos , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/complicações , Melanoma/cirurgia , Pessoa de Meia-Idade , Cirurgia de Mohs/métodos , Mutação , Estadiamento de Neoplasias/métodos , Neprilisina/metabolismo , Neurofibromina 1 , Sarcoma/metabolismo , Sarcoma/cirurgia , Proteína 1 do Complexo Esclerose Tuberosa , Proteína Supressora de Tumor p53 , Melanoma Maligno CutâneoRESUMO
Artificial intelligence (AI) utilizes computer algorithms to carry out tasks with human-like intelligence. Convolutional neural networks, a type of deep learning AI, can classify basal cell carcinoma, seborrheic keratosis, and conventional nevi, highlighting the potential for deep learning algorithms to improve diagnostic workflow in dermatopathology of highly routine diagnoses. Additionally, convolutional neural networks can support the diagnosis of melanoma and may help predict disease outcomes. Capabilities of machine learning in dermatopathology can extend beyond clinical diagnosis to education and research. Intelligent tutoring systems can teach visual diagnoses in inflammatory dermatoses, with measurable cognitive effects on learners. Natural language interfaces can instruct dermatopathology trainees to produce diagnostic reports that capture relevant detail for diagnosis in compliance with guidelines. Furthermore, deep learning can power computation- and population-based research. However, there are many limitations of deep learning that need to be addressed before broad incorporation into clinical practice. The current potential of AI in dermatopathology is to supplement diagnosis, and dermatopathologist guidance is essential for the development of useful deep learning algorithms. Herein, the recent progress of AI in dermatopathology is reviewed with emphasis on how deep learning can influence diagnosis, education, and research.
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Inteligência Artificial/estatística & dados numéricos , Dermatologia/educação , Patologia/educação , Neoplasias Cutâneas/diagnóstico , Algoritmos , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patologia , Aprendizado Profundo/estatística & dados numéricos , Dermatologia/instrumentação , Diagnóstico Diferencial , Testes Diagnósticos de Rotina/instrumentação , Humanos , Ceratose Seborreica/diagnóstico , Ceratose Seborreica/patologia , Aprendizado de Máquina/estatística & dados numéricos , Melanoma/diagnóstico , Melanoma/patologia , Redes Neurais de Computação , Nevo/diagnóstico , Nevo/patologia , Variações Dependentes do Observador , Patologia/instrumentação , Pesquisa/instrumentação , Neoplasias Cutâneas/patologiaRESUMO
ABSTRACT: Multinucleate cell angiohistiocytoma (MCAH) is an uncommon fibrohistiocytic disorder that usually presents as a localized solitary papule or multiple grouped papules. Generalized presentation is very rare with less than 20 cases reported in the literature. In this article, we present histopathological and immunohistochemical studies of 10 lesions from a patient with generalized MCAH. In all lesions, the histopathological changes were confined to a discrete zone of the superficial dermis that consisted of (1) an increase in the number of capillary-sized vessels with thickened walls, (2) presence of oval to dendritic spindle cells and stellate hyperchromatic multinucleated cells, (3) fibrosis marked by compact collagen, (4) hypertrophy and hyperplasia of small nerve fibers, and (5) a moderately dense lymphocytic infiltrate. The entire population of the cellular component including the multinucleated cells stained for CD10, whereas a subpopulation of the mononuclear spindle cells stained for factor XIIIa and CD68. CD34 highlighted only the blood vessels. The results confirm that the multinucleated cells lack expression of CD68 and factor XIIIa and that CD10 may be used to highlight the entire cellular component. The rarely reported hypertrophy and hyperplasia of nerve fibers in MCAH may be a common finding as it was observed in all 10 lesions.
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Histiocitoma Fibroso Maligno/patologia , Neoplasias Cutâneas/patologia , Células Gigantes/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The transcription factor p63 is a homolog of p53, expressed in basal layers of epithelia and myoepithelial cells. Some studies have suggested that p63 may provide utility in differentiating primary versus metastatic mucinous carcinoma of the skin, given its preferential expression in primary adnexal neoplasms. There have been few studies investigating the expression patterns of p40, an isoform of p63, in primary cutaneous mucinous carcinomas. METHODS: An immunohistochemical panel including p40, CK7, CK20, estrogen receptor, and progesterone receptor was applied to primary mucinous carcinomas of the skin, breast, and colon. RESULTS: Only a small subset (25%) of primary cutaneous mucinous carcinomas displayed focal positive staining with p40, similar to what has been reported in the literature for p63. All primary mucinous carcinomas of skin and breast labeled positively with CK7, estrogen receptor, and progesterone receptor. Primary colon mucinous carcinomas were only positive for CK20. CONCLUSIONS: Based on these results, p40 seems to be an insufficient marker for distinguishing primary versus metastatic mucinous carcinoma due to its low rate of positivity in primary cutaneous mucinous carcinomas.
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Adenocarcinoma Mucinoso/patologia , Proteínas de Membrana/metabolismo , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Neoplasias do Colo/patologia , Feminino , Humanos , Masculino , Isoformas de ProteínasRESUMO
ABSTRACT: Various acanthomas have been named based on their distinctive histopathologic patterns. Hypergranulotic dyskeratotic acanthoma represents another acanthoma with a distinctive histopathologic pattern that has been rarely reported. In this article, clinical and histological features of hypergranulotic dyskeratotic acanthoma are delineated. A retrospective analysis was performed of cases with diagnosis or suggested diagnosis of hypergranulotic dyskeratotic acanthoma between 2012 and 2017 from 2 dermatopathology laboratories. Forty-eight potentials were identified, of which 18 cases met the inclusion histologic criteria. Most cases came from women (78%) with a mean age of 53 years, and the thigh was the most common site involved. All cases had the following histopathological findings: (1) verrucous or digitated epidermal hyperplasia, (2) hyperkeratosis dominated by basketweave or compact orthokeratosis, (3) hypergranulosis involving the breadth of the lesion, and (4) presence of enlarged, often indistinctly bordered, keratinocytes with cytoplasm characterized by a blue-gray granular peripheral zone sometimes showing outstretched desmosomes and central perinuclear eosinophilic zones, a combination of findings representing slowly evolving dyskeratosis. Retrospective nature and a small sample size are the major limitations of the study. In sum, hypergranulotic dyskeratotic acanthoma can be easily distinguished from other acanthomas based on their repeatable histopathological findings.
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Acantoma/patologia , Neoplasias Cutâneas/patologia , Acantoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/diagnósticoRESUMO
Fixed drug eruption (FDE) is a cutaneous adverse drug reaction characterized by the onset of rash at a fixed location on the body each time a specific medication is ingested. With each recurrence, the eruption can involve additional sites. Lesions can have overlying vesicles and/or bullae, and when they cover a significant percentage of body surface area, the eruption is referred to as generalized bullous fixed drug eruption (GBFDE). Due to the widespread skin denudation that can be seen in this condition, GBFDE may be confused clinically with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). While treatments described for GBFDE include supportive care, topical and/or systemic steroids, and, recently, cyclosporine, the mainstay of management involves identifying and discontinuing the causative drug. This review article will provide an overview of FDE with an emphasis on its generalized bullous variant.
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Toxidermias , Síndrome de Stevens-Johnson , Diagnóstico Diferencial , Toxidermias/diagnóstico , Toxidermias/etiologia , Humanos , Recidiva , Pele , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/etiologiaRESUMO
The patched tumor suppressor gene (PTCH1) encodes a receptor, which is a key component of the hedgehog signalling pathway. Mutations in PTCH1 are implicated in the development of sporadic basal cell carcinomas (BCC), as well as those in Gorlin Syndrome. Rarely, BCCs may develop in a linear pattern along lines of Blaschko due to cutaneous mosaicism. In cases in which there are other features of Gorlin syndrome, genomic analysis has demonstrated lesional mutations in the Hedgehog signalling pathway. Causative mutations, however, have not been firmly demonstrated in the cases of linear and segmental BCCs in otherwise healthy individuals. Herein, we report a case of a 31 year-old Caucasian woman with linear development of multiple superficial BCCs in a Blaschkoid distribution without other characteristic findings of Gorlin syndrome. Genomic analysis of lesional skin by whole-exome sequencing identified a novel heterozygous mutation PTCH1: NM_000264.3, Exon 15, c.2336-2337insGGTAGGA, p.Asp779Glufs*13 in PTCH1, shared by two discrete samples within the lesion, while no mutations were found in the non-lesional skin or peripheral blood. Given the young age of our patient and linear distribution of BCCs on non-sun exposed skin, our findings suggest segmental mosaicism. The patient was treated with topical 5% imiquimod with histologically confirmed clearance of BCCs in 2 months.
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Carcinoma Basocelular/genética , Mosaicismo , Receptor Patched-1/genética , Neoplasias Cutâneas/genética , Adulto , Carcinoma Basocelular/patologia , Feminino , Heterozigoto , Humanos , Mutação , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Pagetoid Spitz nevus is a rare subtype of Spitz nevus usually found on the lower extremities, particularly on the thigh of women. As a rare and under-recognized entity that can be misdiagnosed as melanoma, further characterization of clinical and histopathological features is needed to improve its recognition. METHODS: A retrospective analysis of all melanocytic neoplasms from the thigh diagnosed over a 3-year period. RESULTS: Fifty-five (15.4%) of the 357 melanocytic neoplasms on the thigh were Spitz nevi, the majority of them occurring in women (87.3%). Of the 55 Spitz nevi, 33 (60.0%) were pagetoid Spitz nevi, 14 (25.5%) were Reed nevi, and eight (14.5%) were conventional Spitz nevi. The mean age of patients with pagetoid Spitz nevi was 47.2, the majority being women (84.9%). Pagetoid Spitz nevi were small, with a mean histopathologic diameter of 4 mm, and often junctional (63.6%). Compared to Clark nevi of the thigh, pagetoid Spitz nevi comprised significantly more solitary melanocytes with a greater degree of scatter. CONCLUSIONS: These results suggest that Spitz nevi and, in particular, pagetoid Spitz nevi constitute a significant percentage of nevi on the thigh. Previously reported benign clinical and histopathological features of pagetoid Spitz nevi are confirmed in this study.
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Síndrome do Nevo Displásico/patologia , Melanócitos/patologia , Nevo de Células Epitelioides e Fusiformes/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Diagnóstico Diferencial , Erros de Diagnóstico , Síndrome do Nevo Displásico/diagnóstico , Epiderme/patologia , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Nevo Pigmentado/diagnóstico , Estudos Retrospectivos , Neoplasias Cutâneas/ultraestrutura , Coxa da Perna/patologiaRESUMO
Toxic erythema of chemotherapy (TEC) is an infrequently reported cutaneous condition, with diagnosis predominately based on clinical presentation, histologic findings, and known reported associations. Therefore, it is important to both recognize common presentations of TEC and be mindful of chemotherapeutic agents associated with this cutaneous side effect to prevent misdiagnosis and prolonged time to treatment. Herein, we present a patient with TEC occurring in intertriginous skin (malignant intertrigo) with classic clinical and histologic findings. In our patient this was associated with a combination neoadjuvant gemcitabine and paclitaxel therapy, a relationship that, to our knowledge, has yet to be reported in the literature.