CIC::DUX4 sarcoma (CDS) is a rare cutaneous and deep soft tissue tumor in the differential diagnosis of small round blue cell sarcomas. CDS, by definition, is negative for rearrangements in EWSR1, and has been reported to have strong nuclear WT1 expression and ETV4 expression in most published cases so far. We herein report a case of challenging CDS diagnosed by genomic profiling, with weak, focal cytoplasmic WT-1 positivity, positive staining for CD56, CD138 (subset), and CD4 (subset). This case highlights the challenges involved in evaluating cutaneous small round blue cell tumors based on morphology and immunohistochemistry alone, especially in the presence of an atypical immunophenotype.

This case report describes a patient with a history of refractory acute myeloid leukemia who presented with white, spiny hyperkeratotic papules on his face and neck, and was subsequently diagnosed with trichodysplasia spinulosa.

With an estimated 3 billion people globally lacking access to dermatological care, technological solutions leveraging artificial intelligence (AI) have been proposed to improve access. Diagnostic AI algorithms, however, require high-quality datasets to allow development and testing, particularly those that enable evaluation of both unimodal and multimodal approaches. Currently, the majority of dermatology AI algorithms are built and tested on proprietary, siloed data, often from a single site and with only a single image type (i.e., clinical or dermoscopic). To address this, we developed and released the Melanoma Research Alliance Multimodal Image Dataset for AI-based Skin Cancer (MIDAS) dataset, the largest publicly available, prospectively-recruited, paired dermoscopic- and clinical image-based dataset of biopsy-proven and dermatopathology-labeled skin lesions. We explored model performance on real-world cases using four previously published state-of-the-art (SOTA) models and compared model-to-clinician diagnostic performance. We also assessed algorithm performance using clinical photography taken at different distances from the lesion to assess its influence across diagnostic categories. We prospectively enrolled 796 patients through an IRB-approved protocol with informed consent representing 1290 unique lesions and 3830 total images (including dermoscopic and clinical images taken at 15-cm and 30-cm distance). Images represented the diagnostic diversity of lesions seen in general dermatology, with malignant, benign, and inflammatory lesions that included melanocytic nevi (22%; n=234), invasive cutaneous melanomas (4%; n=46), and melanoma in situ (4%; n=47). When evaluating SOTA models using the MIDAS dataset, we observed performance reduction across all models compared to their previously published performance metrics, indicating challenges to generalizability of current SOTA algorithms. As a comparative baseline, the dermatologists performing biopsies were 79% accurate with their top-1 diagnosis at differentiating a malignant from benign lesion. For malignant lesions, algorithms performed better on images acquired at 15-cm compared to 30-cm distance while dermoscopic images yielded higher sensitivity compared to clinical images. Improving our understanding of the strengths and weaknesses of AI diagnostic algorithms is critical as these tools advance towards widespread clinical deployment. While many algorithms may report high performance metrics, caution should be taken due to the potential for overfitting to localized datasets. MIDAS's robust, multimodal, and diverse dataset allows researchers to evaluate algorithms on our real-world images and better assess their generalizability. ### Competing Interest Statement AC was an investigator for Skin Analytics. JK is consultant to Hims, Enspectra Health, research collaborator with Google Research, and on advisory board for Skin Analytics. PT received honoraria from Silverchair, unrestricted grants for education projects from Lilly, and honoraria for lectures from AbbVie, Lilly, FotoFinder and Novartis. SSH is the founder, chief executive officer, and chief technical officer of IDerma, Inc. RD has served as an advisor to MDAlgorithms and Revea and received consulting fees from Pfizer, L'Oreal, Frazier Healthcare Partners, and DWA, and research funding from Union Chimique Belge (UCB), and was an investigator for Skin Analytics. RN is a consultant to Enspectra Health and Sanctum, LLC and was an investigator for Skin Analytics. ### Funding Statement This publication is based on research supported by the Melanoma Research Alliance (MRA)- L'Oreal Dermatological Beauty Brands Team Science Award, along with philanthropic funding from the David Mair and Vanessa Vu-Mair Artificial Intelligence in Skin Cancer Fund and the Tal & Cinthia Simon Melanoma Research Fund at Stanford Medicine. We also received a Stanford Human-Centered Artificial Intelligence Google Cloud Credits Grant to support compute efforts. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of Stanford University under IRB#36050 gave ethical approval for this work. Institutional Review Board of Cleveland Clinic Foundation under IRB#20-666 gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data produced are available online at https://stanfordaimi.azurewebsites.net/datasets/f4c2020f-801a-42dd-a477-a1a8357ef2a5

Objectives Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic neoplasm that can show clinical, morphologic, and immunophenotypic overlap with acute myeloid leukemia. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed by myelomonocytic cells previously reported to be reliably absent in BPDCN and proposed as a useful adjunct for the distinction of BPDCN and acute myeloid leukemia. We encountered a case of BPDCN that showed strong nuclear expression of MNDA in bone marrow and breast samples and weak to absent expression in skin samples, prompting us to reevaluate the expression of MNDA in BPDCN.Methods We collected all available BPDCN cases from the Stanford University archives collected in the past 10 years and subjected them to MNDA immunohistochemistry. In select cases, molecular profiling by next-generation sequencing was performed.Results We found 4 cases (of 8 total examined [50%]) with convincing site-discordant MNDA expression. This expression was seen in 3 of 6 (50%) bone marrow samples, 1 of 2 (50%) breast soft tissue samples, and 3 of 14 (up to 21%) skin samples and was not obviously predicted by age, sex, history of myeloid neoplasm, or treatment history. In 2 cases, MNDA was strongly expressed in 2 distinct sites (breast/bone marrow, skin/bone marrow) and negative in subsequent samples.Conclusions Our findings suggest that MNDA expression in BPDCN is anatomic site dependent and transient, with noncutaneous infiltrates showing more frequent expression than cutaneous infiltrates. These results caution against the use of MNDA to exclude BPDCN when considering the differential diagnosis of a blastic extramedullary infiltrate.

Recent advances, accessibility, and adoption of artificial intelligence (AI) increasingly impact dermatology. Understanding how AI is designed, developed, validated, deployed, and monitored will help learners systematically evaluate the technology, research, and clinical utility of these tools. This first of a two-part CME equips dermatologists with the fundamental knowledge of how AI is created and reviews current applications in dermatology. Through increasing AI literacy, this manuscript aims to empower dermatologists to critically analyze and co-create technologies that augment our capacity to provide evidence-based, ethical, and patient-centered care.

Fraction of mutation signatures of mutants with a variant allele frequency less than 20% versus those with an allele frequency between 30% and 45%.

Cytotoxic cutaneous T-cell lymphomas (CCTCLs) are uncommon neoplasms involving skin-tropic T cells expressing cytotoxic markers (e.g. TIA-1, granzyme, and/or perforin). They are comprised of both standalone entities and subsets therein, as defined by the World Health Organization (WHO) fifth edition.1 In addition, we refer to CCTCLs that do not otherwise fit a specific category as cytotoxic cutaneous T-cell lymphoma, not otherwise specified (CCTCL-NOS).2 CCTCLs present variably, with either indolent or aggressive phenotypes, further influenced by disease-related factors such as concurrent hemophagocytic syndrome (HPS).3 Comparatively little is known about the clinical presentation, molecular characterization, and long-term outcomes of patients with CCTCLs; herein, we present a detailed retrospective experience spanning three decades. We reviewed our institution's cutaneous lymphoma database from 1995 to 2020, identifying patients diagnosed with CCTCLs, defined as lymphoproliferative disorders involving the skin with histopathologic expression of at least one cytotoxic marker. Our analysis focused on subcutaneous panniculitis-like T-cell lymphoma (SPTCL), primary cutaneous gamma/delta T-cell lymphoma (PCGDTCL), primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAECTCL), and CCTCL-NOS. Diagnoses were confirmed by expert dermatopathologists (S.F.P., K.R., R.N.). TCR gamma/delta staining was performed where not previously evaluated. Cases with available tissue were tested with a validated high-throughput sequencing panel for hematopoietic neoplasms covering 164 genes (Stanford Heme-STAMP) (Figure S1) and for HAVCR2 coding variants. Clinical data, including suspicion for HPS (defined as documented concern in the medical record based on the collective integration of a patient's clinical and laboratory data) were abstracted via the electronic medical record. Patients with inadequate follow-up were excluded. Regarding treatment, oral corticosteroids used as a temporizing measure prior to definitive therapy were not counted as a distinct line of therapy. Combination therapies (other than multiagent chemotherapy), investigational agents, and drugs used in a singular instance were designated 'other' (Table S1). Radiotherapy started in the midst of an active systemic therapy was not treated as a new line of therapy if the systemic therapy was continued. There are no standardized response criteria for CCTCLs; thus, in lieu of progression-free survival, we measured median time to next treatment (mTTNT), calculated as the start date of one line of therapy to the start date of the next line of therapy. Overall survival (OS) was calculated from date of diagnosis to date of death or last follow-up. Time-to-event outcomes were summarized using Kaplan–Meier curves and inter-group comparisons conducted using log-rank tests. All tests were two-sided, with p < .05 considered significant. Forty-six patients comprised the overall cohort. Twenty-two patients (48%) were diagnosed with SPTCL, 13 (28%) PCGDTCL, 3 (7%) PCAECTCL, and 8 (17%) CCTCL-NOS. Median follow-up from diagnosis was 2.5 years (range: 0.4–10.4). Median age at diagnosis was 59.6 years (range: 14.9–87.4). Sixty-one percent of patients were female and 61% were White. Most patients (87%) presented with generalized skin lesions, while involvement of lymph nodes (22%), viscera (9%), or bone marrow (3%) was uncommon (Table S2). Clinical suspicion for HPS was documented in 23 (50%) patients. Patients received a median of 2.5 lines of therapy (range: 1–12). The most frequently utilized treatments included combination chemotherapy in 18 (39%) patients, pralatrexate in 17 (37%), and romidepsin in 17 (37%). Nine (20%) patients were observed as primary management. Nine (20%) patients underwent allogeneic stem cell transplantation (allo-SCT) (Table S3). In the 22 patients with SPTCL, median age was 44.7 years, and suspicion for HPS was documented in 15 (68%). mTTNT following first- and second-line therapy was 10.2 and 24.0 months, respectively. The most common treatments were combination chemotherapy (n = 9; mTTNT 30.2 months), pralatrexate (n = 7; mTTNT 18.1 months), and romidepsin (n = 9; mTTNT 10.2 months) (Table 1). Four patients with generalized but minimally symptomatic skin involvement were initially observed (mTTNT 19.4 months). Survival outcomes were favorable, with 5-year OS 84% (Figure 1A). Five patients underwent allo-SCT, all with suspected HPS, and all of whom were alive and in remission at last follow-up. In the 13 patients with PCGDTCL, median age was 61.5 years, and suspicion for HPS was present in 6 (46%). mTTNT following first-line therapy was 11.1 months, sharply declining thereafter (Table 1). Initial treatment was heterogeneous, including three patients with generalized but minimally symptomatic skin involvement managed with observation. Two-year OS was 64%. Three patients underwent allo-SCT, all with suspected HPS, and all of whom were alive and in remission at last follow-up. The three patients with PCAECTCL were diagnosed at the median age of 83.2 years and suspicion for HPS was present in two. All three patients died within 18 months of diagnosis. Among the overall cohort, allo-SCT (n = 9) was associated with superior outcomes (2-year OS 100% vs. 66%, p = .03) (Figure 1B). Increasing age negatively impacted survival (2-year OS 42% vs. 100% in patients ≥60 vs. <60 years, respectively, p < .001). Documented clinical suspicion for HPS did not confer a worse outcome (p = .21) (Figure 1C), nor did the presence of lymph node/visceral involvement (p = .50). At last follow-up, 22 (48%) patients remained alive and in remission, 10 (22%) were alive with disease, and 14 (30%) died. Causes of death included lymphoma (n = 8), infection (n = 2), secondary malignancy (n = 1), multiorgan failure (n = 1), mechanical fall (n = 1), and unknown (n = 1). In our cohort of patients with CCTCLs, those with SPTCL exhibited the most favorable outcomes, including patients with low tumor burden, asymptomatic presentations amenable to observation, consistent with prior series.3 For patients requiring treatment, combination chemotherapy and pralatrexate were commonly employed and effective, confirming the previously described activity of chemotherapy, and adding to experiences suggesting pralatrexate may be a preferred option that reasonably balances efficacy and toxicity.4 Prior data have shown that HPS imparts a higher risk of morbidity and mortality in patients with SPTCL.3 While clinical suspicion for HPS was documented in two thirds of our SPTCL cohort, it was not associated with poorer survival (p = .17). This could be explained by our patients more frequently receiving combination chemotherapy, pralatrexate, and allo-SCT—therapies we observed to be most effective. Our data underscore the importance of prioritizing the most potent therapies, including transplant, to optimize outcomes of patients with SPTCL and concurrent HPS. Patients with PCGDTCL and PCAECTCL often presented with widespread, ulcerating skin lesions, and followed an aggressive course with fewer long-term survivors. However, a minority of patients with PCGDTCL exhibited an indolent phenotype and were observed. Patients with aggressive presentations responding to induction therapy and able to proceed to allo-SCT achieved long-term remission, confirming prior descriptions of durable disease control following transplantation in heavily pretreated patients with PCGDTCL.5 In our overall cohort, only two of nine patients receiving allo-SCT were bridged with combination chemotherapy, suggesting that patients with CCTCLs achieving an adequate response to single-agent therapies may be spared more intensive treatment ahead of transplantation. The composition of cases labeled 'CCTCL-NOS' has varied over time amidst nonuniform disease definitions and evolving classification schemes. Our definition included CTCLs expressing at least one cytotoxic marker and not otherwise categorizable under an established WHO entity. For the eight patients in our series, median age was 74.4 years. Suspicion for HPS, laboratory abnormalities, and extracutaneous involvement were uncommon (Table S2). Historical survival statistics in CCTCL-NOS vary, including descriptions of both indolent and aggressive variants. In our cohort, 2-year OS was 71%. Recent work has allowed for improved clinicopathologic distinction of CCTCL-NOS from other defined entities, though additional study is needed to disentangle its heterogeneity.2 Thirteen (26%) patients had targeted DNA sequencing performed; 10 patients (22%; 6 PCGDTCL, 3 CCTCL-NOS, 1 SPTCL) had samples harboring a total of 42 instances of somatic mutations. The most frequent mutations involved TERT (n = 4), and JAK1, FAS, and TP53 (n = 3 each) genes (Table S4). The molecular landscape of CCTCLs is increasingly defined, with disruption of JAK/STAT signaling and abnormalities of chromatin-modifying genes implicated heavily in their pathogeneses.2 Patients in our cohort harbored an array of somatic mutations involving JAK/STAT signaling, epigenetic regulation, signal transduction, and tumor suppressor pathways. The poor outcomes in our patients with PCAECTCL, an entity in which JAK2 aberrations play a critical role,2 offer a rational basis for the exploration of JAK/STAT inhibitors as a novel therapeutic modality in CCTCLs, as has been investigated in PTCLs. Germline variants in HAVCR2, encoding TIM3, have been associated with increased risk of developing SPTCL and a more severe diagnostic category.6 In our cohort, eight patients with SPTCL had germline HAVCR2 testing performed, and one had a HAVCR2 E273K mutation located on exon 7, outside of the classic location on exon 2 (i.e. Y62C, I97M, T101I variants) described previously6; this patient had suspicion for HPS at initial diagnosis. Notably, six of seven patients who tested negative also had suspected HPS. Strengths of this study include its granular examination of clinicopathologic and treatment data, and our primary endpoint of TTNT, a clinically practical measure in rare diseases lacking standardized response criteria. Limitations include the study's retrospective nature, and that some histologic subtypes contained small patient numbers not encompassing the heterogeneity in presentation and management across broader practice settings. Nevertheless, we provide comprehensive data on a defined set of therapeutics that may allow for more confident use of these drugs when encountering such uncommon entities in routine practice. In conclusion, CCTCLs are heterogeneous, and our findings collectively highlight the importance of individualized care, matching treatment intensity to each patient's specific diagnostic, clinical, and molecular phenotype. Project conception: E.M., M.K., and Y.K. Data collection: E.M., S.F.P., K.R., C.J.S., R.W., R.N., W.K.W., M.K., and Y.K. Pathology review: S.F.P., K.R., C.J.S., and R.W. Statistical analysis: S.L. Manuscript preparation and review: All authors. The authors have no relevant disclosures or conflicts of interest. As this was a retrospective study, patient consent was not obtained. All included material herein is original content. The data that support the findings of this study are available from the corresponding author upon reasonable request. Table S1. 'Other' treatment regimens. Table S2. Baseline patient and clinical characteristics, overall and by disease subtype. Table S3. Treatment patterns, overall and by disease subtype. Table S4. Recurring somatic mutations identified by next-generation sequencing (n = 10). Figure S1. List of genes included in the Stanford Tumor Actionable Mutation Panel for Hematopoietic and Lymphoid Neoplasms (Heme-STAMP). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Heatmaps of selected significantly altered pathways. A. Sirtuin signaling. B. Rho signaling C. TP53 signaling.

TERT expression in each histological category.

Correlation between tumor purity as determined by pathology versus as calculated by PURPLE.

This study evaluated the accuracy of ChatGPT in translating English patient education materials into Spanish, Mandarin, and Russian. While ChatGPT shows promise for translating Spanish and Russian medical information, Mandarin translations require further refinement, highlighting the need for careful review of AI-generated translations before clinical use.

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.

Abstract: Mesothelioma of the tunica vaginalis testis (MMTVT) is a rare neoplasm comprising <3% of all cases of malignant mesothelioma (MM). MMTVT derives from the tunica vaginalis testis, an outpouching of the mesothelial-lined abdominal peritoneum that detaches from the abdominal cavity after the descent of the testis. Similar to pleural mesothelioma, asbestos exposure is a known risk factor. However, MMTVT has a better prognosis than pleural mesothelioma. Cutaneous metastases from MMTVT are exceedingly rare. Herein, we describe a case of a 67-year-old man with a history of asbestos exposure presenting with scrotal pain and indurated plaques on his lower abdomen and scrotum. Histologic sections showed a sheet-like dermal proliferation comprising epithelioid cells with necrosis and increased mitotic activity. The clinical and histologic differential diagnosis was broad, including metastatic carcinoma, melanoma, sarcoma, germ cell tumor, hematologic malignancy, neuroendocrine carcinoma, and malignant mesothelioma. By immunohistochemistry, the neoplastic cells were positive for WT1, D2-40, and AE1/AE3, with rare positivity for calretinin, consistent with a diagnosis of mesothelioma. Additional immunohistochemical studies provided no support for the other diagnostic considerations listed above. BAP1 showed retained nuclear expression (normal) by immunohistochemistry. A DNA sequencing panel identified copy number losses in CDKN2A, MTAP, CDKN2B, and NF2, which are frequently identified genetic alterations in malignant mesothelioma. Subsequent testicular imaging demonstrated a diffusely thickened scrotal wall with an enlarged left testicle. Overall, this represents a case of malignant mesothelioma presenting with cutaneous metastases to the scrotum and lower abdomen, with clinical and imaging features suggestive of primary MMTVT. The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

A. PCA plot of all transcriptomes including normal tissues. B. Upset plot of common differentially expressed genes between all histological category comparisons.

Artificial intelligence (AI)-based large language models (LLMs) have been shown to have promising performance in medical applications, including on specialty board examination questions and complex clinical cases ( Beam et al., 2023 Beam K. Sharma P. Kumar B. Wang C. Brodsky D. Martin C.R. et al. Performance of a Large Language Model on Practice Questions for the Neonatal Board Examination. JAMA Pediatr. 2023; 177: 977-979 Crossref Scopus (4) Google Scholar ; Eriksen et al., 2023 Eriksen A.V. Moller S. Ryg J. Use of GPT-4 to Diagnose Complex Clinical Cases. NEJM AI. 2023; 1 Crossref Google Scholar ). Previous reports evaluated the performance of LLMs on dermatology practice board examinations questions ( Passby et al., 2023 Passby L. Jenko N. Wernham A. Performance of ChatGPT on dermatology Specialty Certificate Examination multiple choice questions [e-pub ahead of print]. Clin Exp Dermatol. 2023; https://doi.org/10.1093/ced/llad197 Crossref Google Scholar ; Joly-Chevrier et al., 2023 Joly-Chevrier M. Nguyen A.X. Lesko-Krleza M. Lefrançois P. Performance of ChatGPT on a Practice Dermatology Board Certification Examination. J Cutan Med Surg. 2023; 27: 407-409 Crossref Scopus (2) Google Scholar ; Mirza et al., 2024 Mirza F.N. Lim R.K. Yumeen S. Wahood S. Zaidat B. Shah A. et al. Performance of Three Large Language Models on Dermatology Board Examinations. J Invest Dermatol. 2024; 144: 398-400 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ), but the performance of LLMs compared to practicing dermatologists has not been elucidated. In addition, the use of LLMs by dermatologists and patients relies on the quality of the models' prose (free text) responses rather than multiple-choice selections. Clinical reasoning in model prose responses remains poorly understood in the literature. We conducted the first study, to our knowledge, that assesses the specialty knowledge of a commonly used LLM compared to dermatologists and manually evaluates the quality of model prose responses by board-certified dermatologists.

A 60-year-old woman was referred to Allergy and Immunology for a persistent rash of 9 months. The rash started as mild itching and swelling of the upper lip and eyelid (Figure 1) with "small bumps" on the forehead and chest. The rash would last for several weeks to months, and the eyelid lesion would never fully resolve. The rash would also become exacerbated as weekly "flares" with co-occurring nausea and general malaise. She denied nonsteroidal anti-inflammatory drug or over-the-counter supplement use, had no family history of angioedema, and reported being up-to-date with age-appropriate cancer screenings. Urticaria and angioedema were considered; however, she trialed multiple high-dose H1 and H2 antagonists without relief. Allergic contact dermatitis was also considered for which patch testing was positive for ethylenediamine dihydrochloride on initial read that reportedly self-resolved the following day. She reported partial improvement with systemic corticosteroid tapers, but her rash worsened after their completion. Additional therapies included topical corticosteroids, topical ruxolitinib, montelukast, and 3 months of omalizumab without relief. She then started dupilumab for 4 months, which led to extension of the rash to the bilateral axillae (Figure 2) and scalp. Figure 2Erythematous scaly thin plaques in the bilateral axillary vault. View Large Image Figure Viewer Download Hi-res image

Raw output of pathway prediction between adenomas and carcinomas from Ingenuity Pathway Analysis.

Correlation between tumor purity as determined by pathology and PURPLE versus single base substitution signature abundance (counts) and relative fraction within a sample. A blue line with a light grey confidence interval represents the general linear model for the data points.