From endometrium to fingernail bed: histological evaluation of a rare cutaneous metastasis.

In the dermatological spectrum of oncologic manifestations, cutaneous metastases from endometrial carcinoma stand as a rarity, given the tumour's predilection for neighbouring uterine regions. We present an exceptional case of a patient in her mid-50s, whereby an endometrial carcinoma, defying conventional pathways, manifested on the skin and nail of her distal fourth finger, an unusual site for cutaneous metastases, with a specific histology of the primary cancer.

Revolutionizing diagnostic pathology: The emergence and impact of artificial intelligence-what doesn't kill you makes you stronger?

This study explored the integration and impact of artificial intelligence (AI) in diagnostic pathology, particularly dermatopathology, assessing its challenges and potential solutions for global health care enhancement. A comprehensive literature search in PubMed and Google Scholar, conducted on March 30, 2023, and using terms related to AI, pathology, and machine learning, yielded 44 relevant publications. These were analyzed under themes including the evolution of deep learning in pathology, AI's role in replacing pathologists, development challenges of diagnostic algorithms, clinical implementation hurdles, strategies for practical application in dermatopathology, and future prospects of AI in this field. The findings highlight AI's transformative potential in pathology, underscore the need for ongoing research, collaboration, and regulatory dialogue, and emphasize the importance of addressing the ethical and practical challenges in AI implementation for improved global health care outcomes.

Dupilumab-Associated Sezary Syndrome.

Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD). While recent reports have described cases of new-onset mycosis fungoides (MF) following treatment with dupilumab for AD, to our knowledge only one patient has been delineated with the progression to SS. We present an additional case of a patient who was diagnosed with SS following treatment with dupilumab for adult-onset AD and asthma. We examine SS as a possible side effect of dupilumab while also discussing management and theories to explain this phenomenon.

Dupilumab-associated mycosis fungoides: a cross-sectional study.

Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the progression of mycosis fungoides (MF).This study aims to examine the associations between the length of dupilumab treatment, age and sex, and the onset of MF.An institutional data registry and literature search were used for a retrospective cross-sectional study. Only patients with a diagnosis of MF on dupilumab for the treatment of AD and eczematous dermatitis were included.The primary outcome was the length of dupilumab exposure, age, sex, and the onset of MF. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk.A total of 25 patients were included in this study. Five eligible patients were identified at our institution. In addition, a PubMed review identified an additional 20 patients. At the time of MF diagnosis, the median age was 58, with 42% female. Disease history was significant for adult-onset AD in most patients (n = 17, 65.4%) or recent flare of AD previously in remission (n = 3, 11.5%). All patients were diagnosed with MF, and one patient progressed to Sézary syndrome while on dupilumab, with an average duration of 13.5 months of therapy prior to diagnosis. Tumor stage at diagnosis of MF was described in 19 of the cases and ranged from an early-stage disease (IA) to advanced disease (IV). Treatment strategies included narrow-band UVB therapy, topical corticosteroids, brentuximab, pralatrexate, and acitretin. Male gender, advanced-stage disease, and older age correlated significantly with the hazard of MF onset and a shorter time to onset during dupilumab treatment.Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis, and the shorter the duration of using dupilumab to MF onset. Furthermore, elderly male patients appeared to be more at risk as both male gender and older age correlated with a hazard of MF diagnosis. The results raise the question as to whether the patients had MF misdiagnosed as AD that was unmasked by dupilumab or if MF truly is an adverse effect of treatment with dupilumab. Close monitoring of these patients and further investigation of the relationship between dupilumab and MF can shed more light on this question .

To treat or not to treat: PD-L1 inhibitor-induced keratoacanthoma and squamous cell carcinoma.

Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are rare side effects of programmed cell death ligand-1 (PD-L1) inhibitors that can disrupt therapy. There is no consensus on optimal treatment. We investigated the management strategy and factors influencing pathophysiology. An institutional cancer registry and literature search were used for this retrospective study. Only PD-L1-induced KA and SCC cases were included. Pathology specimens were stained with immune markers and management strategies were analyzed. Four cases were identified at our institution. Immunohistochemistry of atypical keratinocytes revealed PD-1/PD-L1 positivity, high p53, and low bcl-2 for all cases with differential expression of CD44 and beta-catenin for KA versus SCC. Nivolumab was continued or temporarily held with complete resolution. In addition, a literature search identified 30 additional cases of KA/SCC after PDL-1 inhibitor use. The most common treatment was excision/destruction followed by topical and/or intralesional corticosteroids. Therapy was definitely withheld in 22% of KA patients and in 9% of SCC cases. The expression of PD-L1 by atypical keratinocytes helps to explain the effects of nivolumab on the development of cutaneous neoplasms. The expression of immune markers provides mechanistic insights into pathophysiology. Management may be achieved with conservative therapy and without treatment interruption.

Case Presentation: Monkeypox.

Monkeypox is a rare viral disease that initially appeared in West and Central Africa, and is primarily transmitted to humans from animals. It moved to the United States in 2003, which was the first time the disease had left the African continent. It is still uncommon in the United States and elsewhere, although outbreaks have occurred, especially in gay communities,1-3 causing it to be declared a health emergency in some areas. (SKINmed. 2022;20:410-411).

Cutaneous atypical fibroxanthoma with osteoclast-like giant cell: A rare phenomenon.

Atypical fibroxanthoma (AFX) with osteoclast-like giant cells is a rare entity. We present the case of an elderly woman who presented with a pink-purple dome-shaped nodule with central hyperkeratotic crust. Biopsy revealed a cellular, dermal-based tumor comprised of spindle, oval, and osteoclast-like giant cells with pleomorphism. The immunohistochemistry profile supported a diagnosis of AFX with osteoclast-like giant cells. We performed a literature review through PubMed and Google Scholar for AFX with osteoclast-like giant cell formation and found 16 previously reported cases. We aim to provide a review and discuss features of these cases. We also discuss the pathogenesis of these osteoclast-like cells as well as potential pitfalls in diagnosis.

Type III cutaneous atypical meningioma of the scalp.

Meningiomas occur rarely in extracranial sites, including the skin, where they may pose a diagnostic challenge because of their histopathologic overlap with several other spindle-cell tumors. Cutaneous meningiomas are divided into type I (congenital), type II (ectopic), and type III (via direct extension) lesions. We present a rare case of atypical meningioma of the skin in a 71-year-old woman who presented with a painful and enlarging lesion on the left central frontal scalp. Biopsy showed bone and soft tissue with involvement of a spindle cell neoplasm, consisting of whorled nests with atypical features, including variably increased mitotic index, areas of hypercellularity, and sheeted architecture. The overall findings were consistent with an atypical meningioma (World Health Organization grade 2). Atypical meningiomas constitute only 5% to 15% of all meningiomas. Magnetic resonance imaging of the skull later demonstrated a left frontal tumor consistent with an atypical meningioma that had eroded through the skull. Dermatopathologists should consider cutaneous meningioma as a differential diagnosis of spindle-cell neoplasms of the skin and subcutaneous tissue in head and neck.

"Do-not-resuscitate (DNR)" status determines mortality in patients with COVID-19.

We investigatd the influence of do-not-resuscitate (DNR) status on mortality of hospital inpatients who died of COVID-19. This is a retrospective, observational cohort study of all patients admitted to two New Jersey hospitals between March 15 and May 15, 2020, who had, or developed, COVID-19 (1270 patients). Of these, 640 patients died (570 [89.1%] with and 70 [10.9%] without a DNR order at the time of admission) and 630 survived (180 [28.6%] with and 450 [71.4%] without a DNR order when admitted). Among the 120 patients without COVID-19 who died during this interval, 110 (91.7%) had a DNR order when admitted. Deceased positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients were significantly more likely to have a DNR order on admission compared with recovered positive SARS-CoV-2 patients (P < 0.05), similar to those who tested negative for SARS-CoV-2. COVID-19 DNR patients had a higher mortality compared with COVID-19 non-DNR patients (log rank P < 0.001). DNR patients had a significantly increased hazard ratio of dying (HR 2.2 [1.5-3.2], P < 0.001) compared with non-DNR patients, a finding that remained significant in the multivariate model. The risk of death from COVID-19 was significantly influenced by the patients' DNR status.

Long-Term Recurrence of Retroperitoneal Dedifferentiated Liposarcoma After a Complete Surgical Resection: A Report of a Rare Phenomenon.

The objective of this report is to present a rare case of a recurrence after 20 years of retroperitoneal dedifferentiated liposarcoma after surgical resection and to discuss the lessons learned from this rare phenomenon for patients management and understanding the behavior of these aggressive tumors.  A 75-year-old woman presented with recurrent retroperitoneal dedifferentiated liposarcoma who had undergone a surgical resection 20 years earlier and had no evidence of disease on frequent follow-ups during that period. The histopathologic examination revealed different morphologic characteristics between the initial and recurrent presentations. The fluorescence in situ hybridization showed amplification of the mouse double minute 2 homolog (MDM2), a regulator of p53 gene on chromosome 12q15, and positive cyclin-dependent kinase 4 (CDK4) immunostain. Liposarcoma long-term recurrence is a challenging surgical disease to provide the best survival outcome. Incomplete resection could explain the recurrence in anatomic locations where the lesions are intermixed with the neighboring adipose tissue. However, dedifferentiated liposarcoma can rarely recur after 20 years. The molecular transformation and the survival analysis of these tumors predict certain behaviors. The refraction for radiation therapy in our case and the mixed morphology provide some insight into the biology and the clinical management for these aggressive tumors.

What we have learned from the COVID-19 pandemic: Time to think outside the box, maybe far outside.

The coronavirus disease 2019 pandemic has had a profound effect on our lives and careers; this presentation explores some of the lessons we have learned from it and others that it may yet teach us. Socioeconomic effects have been profound, not all of them favorable. Travel and meeting activities, as well as many other activities, have been severely restricted. Social unrest has become intense, and it may have questionable political consequences, as the United States is undergoing a contested election result.

Percutaneous Route of Life: Chylothorax or Total Parenteral Nutrition-Related Bilateral Pleural Effusion in a Neonate?

OBJECTIVE: Peripherally Inserted Central Catheter (PICC) lines are an essential tool in the management of premature neonates. Pleural effusion (PLE) secondary to the leakage of alimentation into the pleural cavity is an encountered complication of central-line total parenteral nutrition (TPN) administration. Methods: We review a case of a premature neonate who suffered large, bilateral PLE after insertion of an upper extremity PICC line for TPN. Results: Pleural fluid biochemical analysis confirmed PICC line infiltration, predominantly with monocytes, low protein, high triglycerides and high glucose. These results favored TPN leakage over chylothorax. Conclusions: To our knowledge, this is the first case of bilateral PLE due to PICC complication in a neonate, which highlights the importance of chylothorax differential diagnosis, the role of autopsy, and the need for clinical precautions when providing premature neonates with high osmolarity TPN.

Pancreatic Carcinosarcoma Clinical Outcome Analysis of the National Cancer Institute Database.

BACKGROUND: Pancreatic carcinosarcomas (PCS) are rare aggressive biphasic malignancies with a poor prognosis. We aimed to improve the understanding of PCS by analyzing variables that influence the mortality of PCS patients. METHODS: The Surveillance, Epidemiology, and End Results database was queried for cases of PCS from 1973 to 2016. Cases were analyzed for patient demographics, tumor characteristics, and surgical intervention. Kaplan-Meier and Cox regression analyses were applied to investigate the overall survival (OS) and prognostic factors. RESULTS: Thirty-nine cases of PCS were identified along with the disease demographics and characteristics. The majority of patients had a regionally invasive or metastatic disease. There was a significant decrease in OS with the increase of the tumor extension. Conversely, surgery showed to improve OS in the crude analysis, including patients that underwent lymphadenectomy. In addition, the unadjusted Cox regression results showed decreased hazard ratios with a local disease versus distant metastasis and with cancer-directed surgery versus no surgery. Nevertheless, the adjusted Cox regression results revealed that metastatic disease was the only significant predictor of survival. CONCLUSIONS: This population-based study provides some insight to a very rare disease by analyzing 39 cases of PCS. Our finding suggests considering PCS as a nonsurgical disease and reserving surgery solely for patients with a localized disease in combination or after neoadjuvant therapy. Consequently, there is a need to further investigate novel therapies for this aggressive malignancy.

Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico.

Targeted therapy has changed the paradigm of advanced NSCLC management by improving the survival rate of patients carrying actionable gene alterations using specific inhibitors. The epidemiologic features of these alterations vary among races. Understanding the racial differences benefits drug development, clinical trial design, and health resource allocation. Compared to Caucasian and Asian populations, current knowledge on Hispanic patients is less and no data of Hispanic patients from Puerto Rico have been reported. We retrieved and analyzed the demographic, clinical, and molecular data of Hispanic NSCLC patients from Puerto Rico with molecular tests performed in the Genoptix Medical Laboratory in Carlsbad, CA, USA between 2011 and 2018. The majority of the NSCLC patients in our study had either adenocarcinoma (75.4%) or squamous cell carcinoma (15.1%). The incidence of EGFR mutations was 24%. They were more common in female and younger patients (<60 years). The deletion of Exon 19 and Exon 21 L858R comprised 55.1% and 31.0% of all EGFR mutations, respectively. The frequency of the T790M mutation was lower compared to that of Hispanic patients reported in the literature (0.5% vs. 2.1%). In addition, 18.7% of the patients were positive for KRAS mutations, which was at the high end of that reported in Hispanic patients. Other driver gene alterations, ALK, MET, RET, ROS1, KRAS, ERBB2, etc., demonstrated similar incidences, as well as gender and age distributions to those previously reported. The KRAS/TP53 and KRAS/STK11 co-mutations were of very low frequencies (3.6%), which could potentially affect the responsiveness to PD1/PD-L1 immunotherapy. Our study demonstrated that the prevalence of NSCLC gene alterations in Hispanic patients from Puerto Rico was comparable to the reported average prevalence in Latin American countries, supporting the intermediate NSCLC gene alteration rate of Hispanic patients between Asian and Caucasian patients. Novel information of the frequencies of KRAS mutation subtypes, driver gene alterations in ROS1, BRAF, and ERBB2, and passenger gene alterations including a rare case with the FGFR2-TACC2 translocation in Hispanic NSCLC patients from Puerto Rico were also described.

Cytogenetic and molecular landscape and its potential clinical significance in Hispanic CMML patients from Puerto Rico.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic neoplasm that exhibits myelodysplastic and myeloproliferative characteristics with heterogeneous clinical and pathological features. There are limited publications on the ethnic and racial disparity of cytogenetics and genomics in CMML patients. This study aims to define the cytogenetic and molecular landscape in Hispanic CMML patients from Puerto Rico and explore its possible clinical significance. One hundred and eleven (111) Hispanic CMML patients from Puerto Rico were diagnosed in our institute from 2009 to 2018. Karyotypes were available in one hundred and seven (107) patients. Seventeen (17) patients had abnormal karyotypes (17/107, 16%). Compared to previously published data, Hispanic CMML patients in this study had significantly lower rates of overall cytogenetic abnormalities (16% vs 27-28%, p < 0.05) and trisomy 8 (2% vs 7%, p < 0.05). Among one hundred and eleven (111) Hispanic CMML patients, 40-gene myeloid molecular profile tests were performed in fifty-six (56) CMML patients. Gene mutations were identified in fifty-four (54) patients (96%). The most frequent mutated genes were: TET2, SRSF2, ASXL1, ZRSR2, DNMT3A, NRAS, CBL, and RUNX1. Twenty-nine (29) out of fifty-six (56) patients (29/56, 52%) had mutated TET2/wild type ASXL1 (muTET2/wtASXL1). Previous studies indicated that mutated ASXL1, DNMT3A, NRAS, RUNX1, and SETBP1 may associate with an unfavorable prognosis and muTET2/wtASXL1 may associate with a favorable prognosis in CMML patients. Compared to previously published data, Hispanic CMML patients from Puerto Rico in this study had significantly lower mutation rates in ASXL1 and SETBP1, and a higher rate of muTET2/wtASXL1. The findings raise the possibility of a favorable prognosis in Hispanic CMML patients.