Application of the model-informed drug development paradigm to datopotamab deruxtecan dose selection for late-stage development.

To replace the conventional maximum tolerated dose (MTD) approach, a paradigm for dose optimization and dose selection that relies on model-informed drug development (MIDD) approaches has been proposed in oncology. Here, we report our application of an MIDD approach during phase I to inform dose selection for the late-stage development of datopotamab deruxtecan (Dato-DXd). Dato-DXd is a TROP2-directed antibody-drug conjugate being developed for advanced/metastatic non-small cell lung cancer (NSCLC) and other tumors.

Folliculocentric lymphocytic hypersensitivity reactions in CLL/SLL patients: A unique clinicopathologic entity amongst non-specific hypersensitivity reactions.

Background: Cutaneous hypersensitivity eruptions in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are a clinically and histologically heterogeneous group that can either precede, occur with, or follow the development of a hematologic malignancy. Therefore, establishing the diagnosis requires careful clinical and pathologic correlation and an understanding of the broad spectrum of presentations. Data is lacking on the correlation of skin disease with molecular/cytogenetic risk profiling of the tumor.

Feasibility of personalized circulating tumor DNA detection in stage II and III melanoma.

The objective of this study was to evaluate the feasibility of developing personalized, tumor-informed assays for patients with high-risk resectable melanoma and examine circulating tumor DNA (ctDNA) levels in relation to clinical status. Pilot prospective study of clinical stage IIB/C and resectable stage III melanoma patients. Tumor tissue was used to design bespoke somatic assays for interrogating ctDNA in patients' plasma using a multiplex PCR (mPCR) next-generation sequencing (NGS)-based approach.

A Single-Institution Cohort Study With Nevi of Special Site: Recurrence, Progression to Melanoma, and Patterns of Management.

Nevi of specialized sites (NOSS) occur on the scalp, ears, flexural, acral, and genital areas and display atypical clinical and histologic features. We assessed NOSS recurrence and progression to melanoma, management patterns, and associations between histologic features and treatment recommendations. We queried all histologic diagnoses of NOSS (n = 275) from 2012 to 2017 from a large U.

Improved overall survival over time in advanced stage mycosis fungoides: a cross-sectional study.

Mycosis Fungoides (MF) is a rare T-cell lymphoma and evidence on treatment practices, and outcomes are limited. We evaluated changes in practice patterns and corresponding effects on overall survival (OS) in MF using a cross-sectional study of patients diagnosed with MF from 2004 to 2016 in the National Cancer Database. Outcomes evaluated included patterns of care and OS across treatment eras.

Histological Transformation and Clonal Relationship of Subcutaneous Marginal Zone B-Cell Lymphoma and Diffuse Large B-Cell Lymphoma.

Histological transformation (HT) is an exceptionally uncommon and poorly understood event where a low-grade or indolent B-cell lymphoma transforms into a more aggressive entity, typically diffuse large B-cell lymphoma (DLBCL). The pathogenesis is unclear; however, HT is associated with a worse prognosis. This article reports a unique case of marginal zone lymphoma (MZL) limited to skin/subcutis (confirmed with PET-CT) that subsequently developed DLBCL, followed by nodal MZL.

Cutaneous T-Cell Acute Lymphoblastic Leukemia and the Expression Pattern of Terminal Deoxynucleotidyl Transferase Immunostaining in Mycosis Fungoides and Spongiotic Dermatitis.

Background/aims: T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, aggressive malignancy that rarely presents in the skin and is generally not considered as part of the differential diagnosis by dermatologists and dermatopathologists. We describe an unusual case of T-ALL presenting with folliculocentric, erythematous papules on the face, histologically resembling mycosis fungoides (MF). Immunostaining for terminal deoxynucleotidyl transferase (TdT) was positive in tumor cells, supporting the diagnosis of cutaneous involvement by T-ALL.

Eosinophils are surprisingly common in biopsy specimens of cutaneous herpes simplex virus and varicella zoster virus infections: Results of a comprehensive histopathologic and clinical appraisal.

Background: While usually straightforward, diagnostic features of cutaneous herpes simplex virus and varicella zoster virus infection (HSV/VZV) are not always present in biopsy specimens. Although intuitively the presence of eosinophils may lead the pathologist away from the diagnosis of cutaneous HSV/VZV infection, in our practice we have noted that eosinophils are often encountered in diagnostic specimens.

Methods: To deduce the frequency with which the inflammatory response accompanying cutaneous HSV/VZV infection includes significant numbers of eosinophils, we performed a retrospective review.

Pretibial Pruritic Papular Dermatitis: A Comprehensive Clinical and Pathologic Review of Cases at a Single Institution.

Background: Studies characterizing clinical and pathologic details of pretibial pruritic papular dermatitis (PPPD) are scarce. Several cases of PPPD at our institution have displayed lymphocyte atypia and CD30 positivity, resembling lymphomatoid papulosis (LyP). We explore the clinical and histological spectrum of PPPD, with emphasis on lymphocyte atypia.

Cutaneous lesions of angioimmunoblastic T-cell lymphoma: Clinical, pathological, and immunophenotypic features.

Background: Angioimmunoblastic T-cell lymphoma (AITL) is a systemic peripheral T-cell lymphoma with a follicular helper T-cell (T ) immunophenotype that frequently involves the skin. However, the histopathology of cutaneous involvement by AITL has not been fully established.

Methods: We reviewed the clinicopathological features of 19 patients seen at our institution with AITL involving the skin.

Cutaneous mantle cell lymphoma histomorphologically mimicking subcutaneous panniculitis-like T-cell lymphoma: Case report.

Secondary cutaneous involvement by mantle cell lymphoma (MCL), an uncommon aggressive B-cell malignancy, predominantly involves the dermis, with few reports of pannicular involvement. Lymphocytic infiltration of subcutaneous tissue is associated with inflammatory panniculitides and certain T-cell lymphomas, primarily subcutaneous panniculitis-like T-Cell lymphoma (SPTCL), which is characterized by rimming of adipocytes by tumor cells. We report the case of a 69-year-old man with a history of systemic nodal MCL who presented with subcutaneous nodules on his lower extremities after receiving multi-agent chemotherapy.

Ominous cutaneous presentation of acute myeloid leukemia without peripheral blood involvement upon initial presentation and relapse: case report and literature review.

Aleukemic leukemia cutis (ALC) is an extremely rare cutaneous manifestation of an aggressive systemic hematological malignancy, associated with dermal infiltration by leukemic cells preceding peripheral blood involvement. This condition is associated with poor outcome, and dermatologists are often responsible for making the initial diagnosis in a timely fashion. To describe a case of ALC and review the literature with an emphasis on the clinical features, summarizing the cutaneous manifestations of this rare systemic disorder.

Similar survival of patients with multiple versus single primary melanomas based on Utah Surveillance, Epidemiology, and End Results data (1973-2011).

Background: Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM).

Objectives: We compared MPM versus SPM patient survival using a matching method that avoids potential biases associated with other analytic approaches.

Methods: Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End Results registry of all melanomas diagnosed or treated in Utah between 1973 and 2011 were reviewed.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis.

Melanoma metastasis to the brain is associated with a poor prognosis. We sought to determine patient demographics and primary tumor factors associated with the development of brain metastasis (BM) and survival. We also investigated whether the BM detection setting (routine screening vs.

Assessment of cabozantinib treatment on QT interval in a phase 3 study in medullary thyroid cancer: evaluation of indirect QT effects mediated through treatment-induced changes in serum electrolytes.

Purpose: This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC).

Methods: Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values.