RESUMO
BACKGROUND: Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. METHODS: BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (TH 1) cells (Tbet), TH 2 cells (Gata3), TH 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. RESULTS: Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll-like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH 2, TH 17, and B-cell immune response. BP-irAE demonstrated a greater density of Tbet+ (TH 1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. CONCLUSIONS: BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal TH 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE.
Assuntos
Penfigoide Bolhoso , Humanos , Vesícula/metabolismo , Proteínas do Sistema Complemento , Imunofluorescência , Perfilação da Expressão Gênica , Imunidade Inata , Penfigoide Bolhoso/patologia , RNA Mensageiro , Receptor 4 Toll-Like/metabolismo , Regulação para CimaRESUMO
ABSTRACT: A 32-year-old G2P1L1 (5 months pregnant) woman presented with a 3-month history of a slow-growing cystic lesion on her scalp vertex. Similar lesions in the exact location were excised twice in the past with a diagnosis of trichilemmal carcinoma (TC). A biopsy of the scalp lesion showed morphology and immunoprofile consistent with previously diagnosed TC. Staging PET/CT demonstrated a 4.7 cm right upper lobe lung, and a subsequent lung biopsy showed a small, round blue-cell tumor with necrosis, morphologically identical to the prior biopsies from the scalp. Considering the unusual clinical course of TC, a lung biopsy was sent for next-generation sequencing that showed EWSR1-FLI1 (type1) fusion. Additionally, CD99 immunostaining revealed uniform cytoplasmic and membranous staining in the tumor cells. The previous scalp excision specimen was also sent for mutation analysis, which showed EWSR1-FLI1 fusion. In conjunction with clinical history and histological and molecular findings, a definitive diagnosis of primary cutaneous Ewing sarcoma (PCES) with local recurrence and metastasis to the lung was made. We present a case of PCES, which was previously misdiagnosed and treated as TC. This case emphasizes the importance of CD99 in the initial screening of cutaneous small round blue-cell tumors to avoid misdiagnosis from other morphological overlaps. Also, despite its rarity, PCES should be included in the differential diagnosis of small, round, blue cell tumors at cutaneous sites. Our case also exemplifies common biases in medical decision-making, including premature closure and anchoring bias which can result in misdiagnosis or diagnostic delay and associated delay in appropriate management.
Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Neoplasias Pulmonares , Sarcoma de Ewing , Sarcoma , Adulto , Feminino , Humanos , Gravidez , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Neoplasias Ósseas/diagnóstico , Diagnóstico Tardio , Pulmão/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Sarcoma/diagnóstico , Sarcoma de Ewing/genética , Couro Cabeludo/patologia , Neoplasias Pulmonares/secundárioRESUMO
ABSTRACT: A 43-year-old woman presented with a palpable, pruritic, minimally painful right vulvar lesion. Physical examination revealed approximately 2.0-cm tender nodule at 70' clock in the right labia majora. Histological sections of the excision specimen showed an unremarkable epidermis with large, well-circumscribed dermal proliferation with extension to the reticular dermis. Within this proliferation are small solid and ductal structures relatively evenly distributed in the sclerotic stroma. The epithelial elements consisted of monomorphous cuboidal cells and assumed round, oval, curvilinear, or have other peculiar geometric shapes, including "comma-like" or "tadpole"-like configurations. The tumor cells were positive for CEA, EMA, and estrogen receptor and negative for progesterone receptor. The clinical presentation and the deep extension of the tumor were similar to the microcystic adnexal carcinoma. Although a syringoma generally presents with multiple lesions and usually involves the superficial dermis, a syringoma with deep extension was favored based on the lack of follicular differentiation, atypia, mitoses, and perineural invasion. Microcystic adnexal carcinoma and syringoma have a morphologic overlap and are misdiagnosed in 30% of the cases. Thus, it is exceptionally important for pathologists to be aware of and be able to distinguish these entities. To the best of our knowledge, this is the first case of a solitary, painful vulvar syringoma with deep extension.
Assuntos
Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Siringoma , Neoplasias Vulvares , Feminino , Humanos , Adulto , Siringoma/diagnóstico , Siringoma/patologia , Neoplasias Cutâneas/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/patologia , Erros de Diagnóstico , Neoplasias das Glândulas Sudoríparas/diagnóstico , Neoplasias das Glândulas Sudoríparas/cirurgia , Neoplasias das Glândulas Sudoríparas/patologiaRESUMO
ABSTRACT: We report an extraordinary case of primary myelofibrosis with transformation to leukemia cutis. A 64-year-old Caucasian man with a history of JAK2-positive primary myelofibrosis presented with erythematous papulonodules on his right lower extremity. A punch biopsy revealed a normal epidermis with an underlying diffuse dermal infiltrate composed of medium-to-large-sized myeloid cells and leukocytes. Neoplastic cells were immunoreactive for LCA, CD34, CD61, CD117, and CD68 and negative for lysozyme, CD20, CD3, myeloperoxidase, and TdT. These findings were consistent with a diagnosis of leukemia cutis. A concurrent bone marrow biopsy demonstrated a markedly fibrotic, hypercellular marrow without a significant increase in blasts. With no morphologic evidence of bone marrow involvement by acute myeloid leukemia, our case suggests that the patient's primary myelofibrosis transformed to leukemia cutis. Our patient died 2 months after the onset of his skin nodules. Our case demonstrates that leukemia cutis should be included in the differential diagnosis for cutaneous nodular lesions in patients with a history of an advanced-stage hematological malignancy.
Assuntos
Leucemia Mieloide Aguda/patologia , Infiltração Leucêmica/metabolismo , Mielofibrose Primária/complicações , Neoplasias Cutâneas/patologia , Evolução Fatal , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/diagnósticoRESUMO
A 15-year-old male presented for evaluation of a volar forearm mass that he noticed four years before. The mass was not painful and his main concern was cosmesis. The mass was two centimeters in diameter with a pinpoint central sinus and scant drainage. After excision, the pathology report noted pilosebaceous units and smooth muscle bundles, consistent with an accessory nipple. In addition, the patient had another accessory nipple in the "milk line" on his torso. While accessory nipples and breast tissue have been reported in numerous locations throughout the body, this is the first reported case of an accessory nipple on the forearm.
RESUMO
Mixed epithelial and stromal tumor (MEST) is a distinctive adult biphasic neoplasm of the kidney characterized by the presence of solid and cystic areas composed of spindled stroma and epithelium lining tubules and cystic spaces respectively. Most MESTs are benign although sarcomatous transformation has rarely been reported. It has not been clearly established whether the epithelial component represents entrapped tubules or constitutes a true neoplastic component. We report an unusual case of a biphasic tumor of the kidney with a benign stroma and a focal component of papillary carcinoma arising in one of the cysts and discuss its pathogenesis.
Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Neoplasias Complexas Mistas/patologia , Idoso , Biomarcadores Tumorais/análise , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Células Estromais/patologiaRESUMO
TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA) using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancer tissues using a combined immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial neoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role). Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5%) of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combined pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. In conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Given the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtyping prostate cancer based on ERG rearrangement status and suggests clinical utility in prostate needle biopsy evaluation.