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PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disorder often arising in pediatric patients. We present a case of an 18-year-old female with a past medical history of growth failure, immunoglobulin A nephropathy, and inflammatory arthritis who presented to a pediatric dermatology clinic with findings of acne, psoriasiform dermatitis, and hidradenitis suppurativa, whose clinical, genetic, and laboratory findings were most consistent with PAMI syndrome. We conducted a literature review to better characterize this rare condition in the context of dermatologic findings. Recognition of the distinctive skin findings seen in PAMI syndrome can help distinguish it from other inflammatory disorders, enabling expedited diagnosis and treatment.
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The diagnosis of cutaneous T-cell lymphoma (CTCL) remains challenging. Demonstration of a clonal T-cell population using T-cell receptor (TCR) gene rearrangement studies by next-generation sequencing (NGS) has been explored in several studies. This review summarizes the current literature on NGS-based sequencing methods for the assessment of TCR clonality in the evaluation of atypical cutaneous lymphoid infiltrates and CTCL on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (lymphoproliferative subgroup). PubMed was searched for relevant articles, including CTCL and NGS, for clonality from 1967 to 2022. Thirteen studies were included in the analysis. The skin was the most commonly assayed compartment with TCR NGS. Sensitivity for TCR NGS in the skin ranged between 69% and 100%, compared to 44%-72% for polymerase chain reaction (PCR)-capillary electrophoresis. Specificity for TCR NGS in the skin ranged from 86% to 100%, compared to 77%-88% for PCR capillary electrophoresis. TCR NGS was also reported to have potential prognostic value in CTCL and can also be used to detect relapse and/or minimal residual disease after treatment.
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Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient's CTCL, which can, in turn, help guide appropriate clinical management.
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Brentuximab Vedotin , Toxidermias , Exantema , Linfoma Cutâneo de Células T , Humanos , Brentuximab Vedotin/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Toxidermias/patologia , Toxidermias/etiologia , Toxidermias/diagnóstico , Idoso , Exantema/induzido quimicamente , Exantema/patologia , Adulto , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/tratamento farmacológico , Imunoconjugados/efeitos adversos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Biópsia , Sequenciamento de Nucleotídeos em Larga Escala , Idoso de 80 Anos ou mais , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Diagnóstico DiferencialRESUMO
Purpose: The term melanocytoma was recently proposed for intermediate-stage melanocytic lesions with specific histopathologic and molecular genetic features. Prior studies have demonstrated a heightened potential for these intermediate lesions to spread to regional lymph nodes, with decreased likelihood for distant spread, when compared to melanomas. Observations: Herein we present a case of a 28-year-old male who presented with a recurrent right lower eyelid margin combined cutaneous and palpebral conjunctival pigmented lesion, ultimately classified as a melanocytoma, to highlight this new nomenclature, characteristic histopathologic and genetic findings, and prognostic implications. Conclusions: Ophthalmologists should be aware of this new cutaneous histopathologic classification system and apply to the periorbital region to improve melanocytic lesion management and surveillance.
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Histological hematoxylin and eosin-stained (H&E) tissue sections are used as the gold standard for pathologic detection of cancer, tumor margin detection, and disease diagnosis. Producing H&E sections, however, is invasive and time-consuming. While deep learning has shown promise in virtual staining of unstained tissue slides, true virtual biopsy requires staining of images taken from intact tissue. In this work, we developed a micron-accuracy coregistration method [micro-registered optical coherence tomography (OCT)] that can take a two-dimensional (2D) H&E slide and find the exact corresponding section in a 3D OCT image taken from the original fresh tissue. We trained a conditional generative adversarial network using the paired dataset and showed high-fidelity conversion of noninvasive OCT images to virtually stained H&E slices in both 2D and 3D. Applying these trained neural networks to in vivo OCT images should enable physicians to readily incorporate OCT imaging into their clinical practice, reducing the number of unnecessary biopsy procedures.
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Redes Neurais de Computação , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Biópsia , Imageamento TridimensionalRESUMO
BACKGROUND: As the use of melanoma antigen recognized by T cells (MART-1) immunohistochemistry (IHC) with Mohs surgery increases for the treatment of melanoma in situ and invasive melanoma, surgeons should be aware of MART-1 staining patterns of incidental lesions often encountered on frozen sections. Lack of this knowledge can lead to unnecessary additional surgery, increased health care costs, and loss of valuable laboratory staff time and resources. OBJECTIVE: To characterize the histopathologic features of incidental lesions encountered during Mohs surgery for melanoma. To review key diagnostic and differentiating features on hematoxylin and eosin staining (H&E) and MART-1 IHC of these lesions. METHODS: A comprehensive review of frozen-section histopathology slides from Mohs cases with MART-1 IHC at our institution was conducted from 2021 to 2023. RESULTS: Incidental benign and malignant lesions were identified and characterized on H&E frozen sections and MART-1 IHC. Although such entities can share MART-1 staining characteristics with melanoma in situ or melanoma, distinguishing characteristics on H&E and lack of histopathologic criteria for melanoma on MART-1 IHC can be used to distinguish these incidental lesions from melanoma. CONCLUSION: Staining of frozen sections for Mohs micrographic surgery with H&E and MART-1 IHC together can differentiate common incidental benign and malignant cutaneous lesions from melanoma.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico , Melanoma/cirurgia , Cirurgia de Mohs , Imuno-Histoquímica , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia , Amarelo de Eosina-(YS)RESUMO
This case report describes an 11-year-old boy with widespread chronic wounds, frequent corneal erosions, dental caries, a tracheostomy, and failure to thrive.
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Epidermólise Bolhosa Juncional , Epidermólise Bolhosa , Humanos , Epidermólise Bolhosa Juncional/complicações , Epidermólise Bolhosa Juncional/diagnóstico , Oxidiazóis , Cicatrização , Epidermólise Bolhosa/complicações , Epidermólise Bolhosa/diagnósticoRESUMO
The important role of the immune system in the surveillance and control of keratinocyte cancers (KCs), namely squamous and basal cell carcinomas, is increasingly appreciated, as new immunotherapies have recently become available. As the field of immunotherapy is rapidly evolving, this review synthesizes key concepts and highlights important cellular components within the immune system responsible for attacking KCs. We review the most current data on the epidemiology, risk factors, and immunotherapy management for KCs. Patients will seek advice from dermatologists to help explain why immunotherapies work for KCs and whether they might be appropriate for different clinical scenarios. Collaboration with medical colleagues across different disciplines to evaluate KCs for response to immunotherapy and early recognition of immune-related adverse events will help to optimize patient outcomes.
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Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/terapia , Carcinoma Basocelular/patologia , Imunoterapia/efeitos adversos , Queratinócitos/patologia , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologiaAssuntos
Esclerose Múltipla , Micose Fungoide , Neoplasias Cutâneas , Humanos , Cloridrato de Fingolimode/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética , Micose Fungoide/tratamento farmacológico , Micose Fungoide/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
ABSTRACT: A previously healthy 2-year-old boy presented with a left sixth cranial nerve palsy. There was a family history of multiple sclerosis and optic neuritis. Neuroimaging showed multiple foci of T2/FLAIR hyperintense signal abnormality in both cerebral hemispheres and in the brainstem. The initial diagnosis was suspicious for demyelinating disease. However, there was no clinical improvement after a course of corticosteroids, and there was no change in his follow-up MRI. He later developed bilateral sixth nerve palsies, with esotropia addressed with bilateral medial rectus botulinum toxin injections. A brain biopsy was planned. However, his 3-month-old sister was separately admitted for fever and pancytopenia. She had markedly elevated ferritin, D-dimer, triglycerides, sIL-2R, CXCL9, and IL-18 and low fibrinogen. Her bone marrow biopsy showed hemophagocytosis. Genetic testing of both siblings revealed biallelic mutations in the PRF1 locus. The final diagnosis of familial hemophagocytic lymphohistiocytosis Type 2 was made. Both siblings underwent chemotherapy. The boy's sixth nerve palsies and MRI abnormalities resolved. Both siblings then went on to undergo bone marrow transplant.
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Doenças do Nervo Abducente , Esotropia , Linfo-Histiocitose Hemofagocítica , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Nervo Abducente , Doenças do Nervo Abducente/diagnóstico , Doenças do Nervo Abducente/etiologia , Doenças do Nervo Abducente/tratamento farmacológico , Medula Óssea , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológicoRESUMO
Cutaneous T-cell lymphomas (CTCL) are a clinically and molecularly heterogeneous class of lymphomas of the skin-homing T cell, and their genetic profiles are not fully characterized. Previously, rearrangements of the Lysine Methyltransferase 2A (KMT2A) gene have been identified as driver mutations only in acute leukemias. KMT2A plays a role in epigenetic regulation, and cancers with such rearrangements are responsive to epigenetic therapy including hypomethylating agents. Here, we report two cases of CTCL with novel genetic profiles. KMT2A rearrangements were identified in two aggressive cases of mycosis fungoides with large cell transformation. A KMT2A::DSCAML1 gene rearrangement was seen in Case 1, while a KMT2A::MAPRE1 fusion was identified in Case 2. These cases demonstrate that KMT2A rearrangements can be found in primary CTCLs rather than solely acute leukemias, illustrating the importance of correlating molecular findings with clinical and histologic features in diagnosis. Additionally, this finding suggests that the subset of CTCLs driven by aberrancy of the KMT2A pathway may be responsive to therapy with hypomethylating agents or menin inhibitors, as seen in acute leukemias.
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Leucemia , Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Humanos , Epigênese Genética , Micose Fungoide/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
Livedoid vasculopathy is a painful thrombo-occlusive vascular disorder characterized by spontaneous thrombosis in medium-size arterioles, which causes localized hypoxia and skin ulceration. As livedoid vasculopathy is rare, case reports are the primary means of expanding collective knowledge about its presentation and response to various therapies.
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Livedo Reticular , Humanos , DorRESUMO
Improved response to canonical therapies requires a mechanistic understanding of dynamic tumor heterogeneity by identifying discrete cellular populations with enhanced cellular plasticity. We have previously demonstrated distinct resistance mechanisms in skin basal cell carcinomas, but a comprehensive understanding of the cellular states and markers associated with these populations remains poorly understood. Here we identify a pre-existing resistant cellular population in naive basal cell carcinoma tumors marked by the surface marker LY6D. LY6D+ tumor cells are spatially localized and possess basal cell carcinoma and squamous cell carcinoma-like features. Using computational tools, organoids, and spatial tools, we show that LY6D+ basosquamous cells represent a persister population lying on a central node along the skin lineage-associated spectrum of epithelial states with local environmental and applied therapies determining the kinetics of accumulation. Surprisingly, LY6D+ basosquamous populations exist in many epithelial tumors, such as pancreatic adenocarcinomas, which have poor outcomes. Overall, our results identify the resistant LY6D+ basosquamous population as an important clinical target and suggest strategies for future therapeutic approaches to target them.
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Carcinoma Basocelular , Física , Humanos , Moléculas de Adesão Celular , Proteínas Ligadas por GPIRESUMO
Importance: There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date. Objective: To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions. Design, Setting, and Participants: This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort was classified as (1) SPTCL or (2) adipotropic lymphoproliferative disorder (ALPD) for similar cases with incomplete histopathological criteria for SPTCL designation. Exposures: Cases of SPTCL diagnosed between 1998 and 2018. Main Outcomes and Measures: The main outcome was disease presentation and evolution, including response to therapy, disease progression, and development of hemophagocytic lymphohistiocytosis. Results: The cohort of 95 patients (median [range] age, 38 [2-81] years; female-to-male ratio, 2.7) included 75 cases of SPTCL and 20 cases of ALPD. The clinical presentation was similar for both groups with multiple (61 of 72 [85%]) or single (11 of 72 [15%]) tender nodules mostly involving extremities, occasionally resulting in lipoatrophy. Hemophagocytic lymphohistiocytosis (HLH) was only observed in SPTCL cases. With a mean follow-up of 56 months, 60 of 90 patients (67%) achieved complete remission with a median (range) of 3 (1-7) cumulative therapies. Relapse was common. None of the patients died of disease progression or HLH. Two patients with ALPD eventually progressed to SPTCL without associated systemic symptoms or HLH. Conclusions and Relevance: In this case series of patients initially diagnosed as having SPTCL, results showed no evidence of systemic tumoral progression beyond the adipose tissue. The SPTCL experience in this study confirmed an indolent course and favorable response to a variety of treatments ranging from immune modulation to chemotherapy followed by hematopoietic stem cell transplantation. Morbidity was primarily associated with HLH.