Chronic ulcer in a patient with essential thrombocythemia taking hydroxyurea.

Chronic skin ulcers in patients with suspected pyoderma gangrenosum can, on closer inspection and further workup, have a different cause. Recognition of key features on clinical examination such as the presence of atrophie blanche is key to avoid misdiagnosis of pyoderma gangrenosum and its subsequent treatment with high-dose corticosteroids and other immunosuppressive medications.

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

A case report of recurrent primary posterior mediastinal perivascular epithelioid cell tumour compressing the right inferior pulmonary vein, atria, and inferior vena cava.

Background: Perivascular epithelioid cell tumours (PEComas) are rare soft tissue neoplasms that commonly occur in the uterus, skin, and liver and less commonly in the retroperitoneum, colon, and mediastinum. Case summary: A 36-year-old male patient with a history of mediastinal PEComa status post resection, essential hypertension, and atrial fibrillation status post appendage ligation currently not on anticoagulation presented with a 1-week history of fevers, chills, productive cough, chest pain, dyspnoea on exertion, loss of appetite, and general weakness. Vital signs, physical exam, laboratory data, electrocardiogram, and chest radiograph were grossly unremarkable. A multimodality imaging approach utilizing transthoracic echocardiogram, transoesophageal echocardiogram (TEE), cardiac magnetic resonance imaging (cMRI), and computed tomography angiography of the chest, abdomen, and pelvis revealed a local 40 mm × 53 mm globular bilobed vascularized scar-free posterior mediastinal mass arising from the roof of the left and right atria and extending superiorly to the main pulmonary artery and inferiorly to the inferior vena cava. Based on the mass' size and proximity to vital structures and tumour recurrence, the case was presented during tumour board rounds, and the outcome was to surgically resect the mass and then have the patient follow up with medical oncology and radiation oncology for possible chemotherapy and radiation, respectively. Discussion: Perivascular epithelioid cell tumours are rare, and mediastinal PEComas are even rarer, warranting a multimodality imaging approach involving TEE and cMRI and a multidisciplinary approach involving anaesthesiologists, cardiologists, cardiothoracic surgeons, medical oncologists, pathologists, radiologists, and radiation oncologists.

Risk of Multiple Primary Cancers in Patients With Merkel Cell Carcinoma: A SEER-Based Analysis.

Importance: The risk of subsequent primary cancers after a diagnosis of cutaneous Merkel cell carcinoma (MCC) is not well established. Objective: To evaluate the risk of subsequent primary cancers after the diagnosis of a first primary cutaneous MCC. Design, Setting, and Participants: This cohort study analyzed data from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program from January 1, 2000, to December 31, 2019. In all, 6146 patients diagnosed with a first primary cutaneous MCC were identified. Main Outcomes and Measures: The primary outcome was the relative and absolute risks of subsequent primary cancers after the diagnosis of a first primary MCC, which were calculated using the standardized incidence ratio (SIR; ratio of observed to expected cases of subsequent cancer) and the excess risk (difference between observed and expected cases of subsequent cancer divided by the person-years at risk), respectively. Data were analyzed between January 1, 2000, and December 31, 2019. Results: Of 6146 patients with a first primary MCC diagnosed at a median (IQR) age of 76 (66-83) years, 3713 (60.4%) were men, and the predominant race and ethnicity was non-Hispanic White (5491 individuals [89.3%]). Of these patients, 725 (11.8%) developed subsequent primary cancers, with an SIR of 1.28 (95% CI, 1.19-1.38) and excess risk of 57.25 per 10 000 person-years. For solid tumors after MCC, risk was elevated for cutaneous melanoma (SIR, 2.36 [95% CI, 1.85-2.97]; excess risk, 15.27 per 10 000 person-years) and papillary thyroid carcinoma (SIR, 5.26 [95% CI, 3.25-8.04]; excess risk, 6.16 per 10 000 person-years). For hematologic cancers after MCC, risk was increased for non-Hodgkin lymphoma (SIR, 2.62 [95% CI, 2.04-3.32]; excess risk, 15.48 per 10 000 person-years). Conclusions and Relevance: This cohort study found that patients with MCC had an increased risk of subsequently developing solid and hematologic cancers. This increased risk may be associated with increased surveillance, treatment-related factors, or shared etiologies of the other cancers with MCC. Further studies exploring possible common etiological factors shared between MCC and other primary cancers are warranted.

Elevated Risk of Visceral Malignant Neoplasms in Extramammary Paget Disease.

This cross-sectional study evaluates the incidence and types of cancers that develop years after an extramammary Paget disease (EMPD) diagnosis.

Comparison of clinicopathologic features, survival, and demographics in sebaceous carcinoma patients with and without Muir-Torre syndrome.

BACKGROUND: Visceral malignancies in patients with Lynch syndrome behave less aggressively than in those without Lynch syndrome. The behavior of sebaceous carcinoma (SC) in Muir-Torre syndrome (MTS), a variant of Lynch syndrome, is incompletely investigated. OBJECTIVE: To investigate features and survival of SC patients with and without MTS. METHODS: Retrospective cohort study in the Surveillance, Epidemiology, and End Results 17 database from 2000 to 2019 of patients with SC. Patients were classified as MTS or non-MTS cases based on a threshold score of 2 on the Mayo MTS risk score. RESULTS: We identified 105 (2.8%) MTS cases and 3677 (97.2%) non-MTS cases. On univariate analysis, MTS patients were younger, had a higher proportion of tumors outside the head/neck, and had fewer high-grade tumors. On Kaplan-Meier analysis, MTS patients trended toward having better SC-specific survival. On multivariate Cox proportional hazards analysis adjusting for other covariates, MTS status was an independent predictor of worse overall survival. However, there was no association between MTS status and SC-specific survival. LIMITATIONS: Given relatively high disease-specific survival in SC, our study may have been underpowered to detect a difference on Kaplan-Meier analysis. CONCLUSIONS: Our study suggests SC does not behave more aggressively in patients with MTS.

Health Care Utilization and Costs in Systemic Therapies for Metastatic Melanoma from 2016 to 2020.

BACKGROUND: Widespread implementation of immune checkpoint inhibitors (ICI) and targeted therapies for metastatic melanoma has led to a decline in melanoma-related mortality but increased healthcare costs. We aimed to determine how healthcare utilization varied by systemic, non-adjuvant melanoma treatment from 2016 to 2020. PATIENTS AND METHODS: Adults with presumed stage IV metastatic melanoma receiving systemic therapy from 2016 to 2020 were identified in Optum, a nationwide commercial claims database. Treatment groups were nivolumab, pembrolizumab, ipilimumab+nivolumab (combination-ICI), or BRAF+MEK inhibitor (BRAFi+MEKi) therapy. Outcomes included hospitalizations, days hospitalized, emergency room (ER) visits, outpatient visits, and healthcare costs per patient per month (pppm). Multivariable regression models were used to analyze whether cost and utilization outcomes varied by treatment group, with nivolumab as reference. RESULTS: Among 2018 adult patients with metastatic melanoma identified, mean (SD) age was 67 (15) years. From 2016 to 2020, nivolumab surpassed pembrolizumab as the most prescribed systemic melanoma therapy while combination-ICI and BRAFi+MEKi therapies remained stable. Relative to nivolumab, all other therapies were associated with increased total healthcare costs (combination-ICI: ß = $47 600 pppm, 95%CI $42 200-$53 100; BRAFi+MEKi: ß = $3810, 95%CI $365-$7260; pembrolizumab: ß = $6450, 95%CI $4420-$8480). Combination-ICI and BRAFi+MEKi therapies were associated with more inpatient hospital days. CONCLUSIONS: Amid the evolving landscape of systemic therapy for advanced melanoma, nivolumab monotherapy emerged as the most used and least costly systemic treatment from 2016 to 2020. Its sharp increase in use in 2018 and lower costs relative to pembrolizumab may in part be due to earlier adoption of less frequent dosing intervals.

Pigmented PRRX1::NCOA1-rearranged fibroblastic tumor: A rare morphologic variant of an emerging mesenchymal tumor.

PRRX::NCOAx-rearranged fibroblastic tumor is a recently described, morphologically distinctive subcutaneous fibroblastic tumor with benign behavior. To date, 12 cases have been reported. Here, we report a new case of PRRX::NCOAx-rearranged fibroblastic tumor showing a prominent pigmented component. The lesion occurred on the shoulder of a 23-year-old male. It was an at least 2.5 cm subcutaneous tumor with a multinodular and plexiform appearance. Morphologically, the tumor was characterized by a variably cellular proliferation of uniform oval to spindle cells arranged in fascicles and cords within a myxocollagenous stroma. Irregular, elongated, dilated vessels were prominent at the periphery of tumor nodules. In addition, nests and clusters of pigment-laden epithelioid and dendritic cells were present. Immunohistochemically, the non-pigmented tumor cells showed patchy positivity for factor XIIIa and focal positivity for S100 protein. The pigmented cells were positive for S100 protein, SOX10, MITF, and a pan-melanocytic cocktail (Melan-A, HMB-45, and tyrosinase). Next-generation RNA sequencing identified an in-frame PRRX1::NCOA1 fusion. In summary, this case highlights a rare pigmented variant of PRRX::NCOAx-rearranged fibroblastic tumor, expanding the morphologic spectrum of this newly described mesenchymal tumor.

SATB2 Expression in Undifferentiated Pleomorphic Sarcomas of Bone.

OBJECTIVES: SATB2 is a transcriptional regulator that plays an important role in osteoblastic differentiation. We examined the prevalence and potential significance of SATB2 expression in undifferentiated pleomorphic sarcoma (UPS) of bone. METHODS: We examined 38 cases of bone UPS without osteoid. The male-to-female ratio was 1:1.4, with a median age of 48 years (range, 23-83 years). Tumors occurred primarily in the femur (n = 8) and ilium (n = 8), with a median tumor size of 9.5 cm (range, 1.8-27.0 cm). The median follow-up was 24.7 months (range, 2-82 months): 11 patients developed local recurrences, and 18 patients had metastases, mainly to lung and bone. RESULTS: SATB2 expression (nuclear labeling ≥5%) was seen in 21 of 38 (55%) cases: 5 with focal (nuclear labeling 5%), 11 with patchy (nuclear labeling 5%-50%), and 5 with diffuse (nuclear labeling ≥50%) staining. Among this group, diffuse SATB2 expression demonstrated superior metastasis-free survival (P = .036) and event-free survival (P = .024). For comparison, 100 soft tissue UPS were stained; the majority were negative (75/100 [75%]). CONCLUSIONS: UPS of bone demonstrated more frequent SATB2 expression compared with its soft tissue counterpart. In this series, diffuse SATB2 expression in UPS of bone was associated with better outcomes. Additional studies are still needed to determine its significance.

Dedifferentiated chondrosarcoma with minimal or small dedifferentiated component.

Dedifferentiated chondrosarcoma (DDCS) is an aggressive bone sarcoma characterized by low-intermediate grade cartilage component with abrupt transition to a high-grade non-chondrosarcomatous component. Generally, the dedifferentiated (DD) component is large. However, rare cases have minimal (<1 cm) or small (1-2 cm) areas of DD. We describe the clinicopathologic features of such tumors and evaluate the prognostic significance of this finding compared to cases with large DD (>2 cm). Available slides were re-reviewed for assessment of histologic features. The medical record was reviewed for imaging studies and clinical characteristics. Thirty-five cases were included. Six patients had minimal DD, four had small DD and 25 had large DD. None of the minimal DD showed definitive imaging evidence of DD. Two minimal DD (33%) locally recurred and 2 (33%) developed distant metastases. None of the small DD cases showed definitive imaging evidence of DD. None of the small DD locally recurred and at least 1 (25%) developed distant metastases. There was no significant difference in age, gender, pelvic site, tumor size >8 cm, tumor necrosis or undifferentiated pleomorphic sarcoma-like morphology between minimal or small DD compared to large DD, though osteosarcomatous differentiation was significantly more common in large DD. There was no significant difference in overall survival between minimal or small DD compared to large DD (p = 0.81 and p = 0.17, respectively), or in progression-free survival (p = 0.47 and 0.29, respectively), or metastasis-free survival (p = 0.06 and 0.62, respectively). DDCS with minimal or small DD show similar demographic distribution, anatomic localization and histologic features to large DD. DD in these cases is unlikely to be detected on imaging. Furthermore, at least a subset of these tumors is extremely aggressive despite the limited extent of DD. This highlights the need for thorough gross and histologic examination and sampling.