Histopathologic Findings of Evolving Mpox Lesions.

ABSTRACT: This article reports two cases of the 2022 mpox virus with notable histopathology, and includes a novel description of mpox pseudotumor in the perianal region which is not previously described. This article additionally includes literature review of characteristic histopathology through evolving lesions, as it is sparsely described in relation to the 2022 mpox outbreak. Case one describes a 42-year-old man who presented with umbilicated, smooth papules on the trunk and extremities, and milia-like papules on the face. Histopathology of an umbilicated lesion revealed epidermal acanthosis with keratinocyte pallor, ballooning degeneration, keratinocyte necrosis, and neutrophilic epitheliotropism. Case two describes a 51-year-old man who presented with scattered eroded papules as well as a perianal mass. Histopathology of the mass revealed ulceration with keratinocyte enlargement and pallor with a mixed inflammatory cell infiltrate. It additionally revealed rare multinucleated keratinocytes with nuclear molding. These cases are remarkable and contribute to literature as reports of the histopathology of the atypical 2022 mpox outbreak are rare. A combination of clinical, laboratory, and histopathologic evidence is useful in diagnosing mpox, and these cases contribute to describing the evolution of viral lesions.

The effect of histopathologic analysis and tissue cultures on inpatient management of cellulitis: a randomized control trial.

BACKGROUND: In the absence of a gold-standard diagnostic modality for cellulitis, sterile inflammatory disorders may be misdiagnosed as cellulitis. OBJECTIVE: To determine the utility of skin biopsy and tissue culture for the diagnosis and management of patients admitted with a diagnosis of presumed cellulitis. DESIGN: Pilot single-blind parallel group randomized controlled clinical trial in 56 patients with a primary diagnosis of presumed cellulitis. In the intervention group only, skin biopsy and tissue culture results were made available to the primary care team to guide diagnosis and management. Length of hospital stay and antibiotic use were evaluated as outcome measures. RESULTS: Length of stay showed the greatest opportunity for further study as a primary outcome (intervention: 4, IQR (2-6) vs. control: 5 IQR (3-8) days; p = 0.124). LIMITATIONS: The COVID-19 pandemic placed limitations on participant enrollment and study duration; in addition, data was collected from a single medical center. CONCLUSION: This study demonstrates that length of stay and anti-pseudomonal antibiotic de-escalation are endpoints that may be influenced by biopsy and tissue culture results in presumed cellulitis patients; these outcomes warrant further study.

Acute Interstitial Inflammation on Skin Biopsies and Positive Tissue Cultures in Cellulitis Patients Are Associated a Worse Prognosis.

BACKGROUND: Cellulitis is a significant public health burden and lacks a gold standard for diagnosis. Up to 1/3 of patients are incorrectly diagnosed. The skin biopsy has been proposed as the gold standard. OBJECTIVE: In this study, we evaluate the histopathologic characteristics and tissue culture positivity of biopsies in patients diagnosed with cellulitis seen by our inpatient dermatology consultation service. METHODS: This retrospective cohort study examined patients who were hospitalized with a skin and soft tissue infection at our institution between 2011 and 2020 and underwent a skin biopsy. RESULTS: Those with a positive tissue culture were more likely to die within 30 days compared with those with negative tissue cultures (26% vs. 6%, P = 0.048). Patients who died within 30 days were more likely to have acute interstitial inflammation as a feature on histopathology (38%, P = 0.03). LIMITATIONS: Single institutional design, unintentional exclusion of patients with organism-specific diagnosis, and selection for a medically complex patient population because of the nonroutine collection of biopsies. CONCLUSION: Positive tissue cultures and histopathology showing acute interstitial space inflammation on skin and soft tissue infection (SSTI) biopsies are associated with increased mortality and thus may serve as indicators of poor prognosis.

Impact of Cutaneous Squamous Cell Carcinoma Histologic Features on Percent Interrater Agreement Regarding Tumor Differentiation.

BACKGROUND: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system. OBJECTIVE: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement. MATERIALS AND METHODS: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system. RESULTS: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study. CONCLUSION: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading.

TTK inhibitor OSU13 promotes immunotherapy responses by activating tumor STING.

TTK spindle assembly checkpoint kinase is an emerging cancer target. This preclinical study explored the antitumor mechanism of TTK inhibitor OSU13 to define a strategy for clinical development. We observed prominent antitumor activity of OSU13 in melanoma, colon and breast cancer cells, organoids derived from patients with melanoma, and mice bearing colon tumors associated with G2 cell cycle arrest, senescence, and apoptosis. OSU13-treated cells displayed DNA damage and micronuclei that triggered the cytosolic DNA-sensing cGAS/STING pathway. STING was required for the induction of several proteins involved in T cell recruitment and activity. Tumors from OSU13-treated mice showed an increased proportion of T and NK cells and evidence of PD-1/PD-L1 immune checkpoint activation. Combining a low-toxicity dose of OSU13 with anti-PD-1 checkpoint blockade resulted in prominent STING- and CD8+ T cell-dependent tumor inhibition and improved survival. These findings provide a rationale for utilizing TTK inhibitors in combination with immunotherapy in STING-proficient tumors.

Observation of lymphadenopathy, systemic symptoms, and treatment in suspected indolent cutaneous B-cell lymphomas.

BACKGROUND: Following the initial diagnosis of a marginal zone or follicle center lymphoma on skin biopsy, patients undergo staging to determine the extent of disease. OBJECTIVE: We sought to characterize the frequency that these patients were found to have a systemic nodal disease upon work-up as well as the impact of imaging on disease management. METHODS: We conducted a retrospective chart review of patients presenting with a working diagnosis of PCMZL or PCFCL treated at The Ohio State University from 1990 to 2022. Data collected included: patient history, progress notes, virtual encounters, laboratory results, presentation features, imaging, and pathology. Biomarkers included ANA, SSA/SSB, BCL6 and H. Pylori labs, bone marrow biopsies, positive imaging, and need of systemic medication and mortality. RESULTS: 71 patients with suspected PCMZL and PCFCL were identified. 66 of 71 patients underwent imaging. Of this group, 12 patients (9 with suspected PCFCL and 3 with suspected PCMZL) demonstrated lymphadenopathy on imaging. Of these 12 patients, 5 underwent biopsy of suspected lymph nodes, and 3 had biopsy-proven nodal involvement and received systemic therapy. Of the remaining 7 patients with evidence of lymphadenopathy on imaging, 4 were thought to have reactive lymph nodes, and 3 were treated empirically with systemic chemotherapy due to the extent or progression of their disease. Of patients with imaging negative for lymphadenopathy, 3 of 52 (5.8%) patients with received systemic treatment, while 49 of 52 patients (94.2%) received localized treatment. LIMITATIONS: Most of the relationships between this data were correlational and patients selected for this study were limited to a single institution. CONCLUSION: Prospective study of the role of imaging without subsequent lymph biopsy to direct treatment decisions is warranted.

Myeloid neoplasm with histiocytosis and spleen tyrosine kinase fusion responds to fostamatinib.

Not available.

Symmetrical drug-related intertriginous and flexural exanthema with high-risk systemic features: a unique clinical phenotype in hospitalized patients.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is classically considered a low-risk, self-limiting eruption lacking systemic manifestations and sparing facial and mucosal areas. We present 7 inpatients meeting diagnostic criteria for SDRIFE with concomitant systemic manifestations ± high-risk facial involvement acutely after antibiotic exposure (mean latency 6.71 days). These cases deviate from classic, self-limited SDRIFE and represent a unique phenotype of SDRIFE, characterized by coexisting extracutaneous manifestations. Onset of systemic stigmata coincided with or preceded cutaneous involvement in 4 and 3 patients, respectively. All patients developed peripheral eosinophilia and 6 patients had ≥ 2 extracutaneous systems involved. Facial involvement, a high-risk feature associated with severe cutaneous adverse reactions but atypical in classic SDRIFE, occurred in 4 cases. Patients had favorable clinical outcomes following drug cessation and treatment with 4-6 week corticosteroid tapers. We suggest that baseline labs be considered in hospitalized patients with antibiotic-induced SDRIFE. These patients may also necessitate systemic therapy given extracutaneous involvement, deviating from standard SDRIFE treatment with drug cessation alone.

Drug Reaction With Eosinophilia and Systemic Symptoms With Pustulosis.

This cohort study examines patients with drug reaction with eosinophilia and systemic symptoms who also have pustules.

Graduate medical education success coaching for residents and fellows: a single-institution real-world experience.

While coaching has been employed as a success strategy in many areas such as athletics and business for decades, its use is relatively new in the medical field despite evidence of its benefits. Implementation and engagement regarding coaching in graduate medical education (GME) for residents and fellows is particularly scarce. We report our three-year experience of a GME success coaching program that aims to help trainees reach their full potential by addressing various areas of medical knowledge, clinical skills, efficiency, interpersonal skills and communication, professionalism, and mental health and well-being. The majority of participants (87%) were identified by themselves, their program director, and/or the GME coaches to have more than one area of need. The majority (79%) of referrals were identified by the coaches to have additional needs to the reasons for referral. We provide a framework for implementation of a GME coaching program and propose that coaching in GME may provide an additional safe environment for learners to reveal areas of concerns or difficulty that otherwise would not be disclosed and/or addressed.