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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.

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

Importance: Treating AD with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with progression of MF. Objective: To examine the associations between length of dupilumab treatment, age and sex, and onset of MF. Design, Setting, and Participants: 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. Exposure: AD patients treated with dupilumab. Main Outcomes and Measures: The primary outcome was the length of dupilmab exposure, age and sex, and MF onset. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk. Results: Five eligible patients were identified at our institution. In addition, the PubMed review identified an additional 20 patients. The median age was 58 years, 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 Sezary syndrome while on dupilumab, with an average duration of 13.5 months of therapy prior to diagnosis. Tumor stage 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, praladextrate, 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. Conclusion and Relevance: Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis 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 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 into this question.

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.

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.

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.

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.

Ameloblastoma is a benign locally invasive tumor with a high tendency to recur. It is considered rare in the pediatric population, with most cases diagnosed in the third to fifth decades of life. Approximately 80% of ameloblastomas occur in the molar and ramus region of the mandible, while 20% of cases occur in the maxillary posterior region. This report presents a case of plexiform ameloblastoma in an uncommon location in an 8-year-old child. The lesion was initially thought to be a dentigerous cyst, based on its location and radiographic appearance. The clinical and radiographic features, histopathology, and treatment of solid, plexiform, maxillary ameloblastoma are reviewed, with an added emphasis on a literature review of ameloblastoma in children. This report emphasize the importance of long-term follow-up, since recurrence may occur many years after initial tumor removal.

The objective of this report is to present a rare case of primary cutaneous mucinous carcinoma (PCMC) manifesting with granuloma annulare (GA), and to discuss the association as a paraneoplastic phenomenon. A 65-year-old female presented with a painless, slow-growing, cystic nodule less than 1 cm over the left lateral canthus. The clinical presentation was highly suspicious of sebaceous cyst. The histopathologic examination revealed variable sizes of neoplastic cell clusters in a pool of abundant mucin. A focus of palisading lympho-histiocytic infiltrate surrounding a necrobiosis suggestive of granuloma annulare adjacent to the tumor is identified. Series of extensive investigations performed did not reveal any primary origin. GA can rarely be associated with various malignant conditions. Its association and prognostic importance to these conditions are unclear. The presence with certain malignancies and the resolution of GA with the treatment of underlying malignancy are an indicator that this condition can very well be a paraneoplastic phenomenon.

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 (&lt, 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.

Although pityriasis alba is a common dermatologic condition, its pathogenesis is poorly understood, and there are many discrepancies in the literature. To assess the effect of the duration of disease on the histologic findings, a search of cases labeled "pityriasis alba" was performed on any cases submitted to our dermatopathology laboratory. Of 179 cases of pityriasis alba, five cases identified the duration of the disease, when the biopsy was taken. A biopsy for a lesion of only 1-month duration demonstrated groups of large, prominent melanocytes heaped up upon one another. Compared with biopsies from patients who had the lesions for increasingly longer periods of time, it was apparent that the melanocytes became progressively less abundant and smaller with less prominent dendritic processes. The time that the biopsy is taken may affect the histologic findings of pityriasis alba. Additionally, an abundance of melanosomes was observed between the melanocytes in all sections examined which may reflect a problem with the transfer of melanosomes into keratinocytes in this condition.

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.

Endosalpingiosis is the presence of ectopic Müllerian-type epithelium resembling Fallopian tube epithelium. It usually appears as small glandular inclusions in various peritoneal sites or lymph nodes. Rarely, it is papillary in configuration, and lack of familiarity with this entity could lead to overinterpretation as a malignancy. We recently encountered a case of papillary endosalpingiosis found incidentally at laparotomy for ectopic pregnancy. Awareness of this entity is important, as it may be a diagnostic challenge.

Immunotherapy agents such as cytotoxic T-lymphocyte antigen-4 and programed cell death protein-1 inhibitors show efficacy in cancer therapy but are associated with immune-related adverse events. It commonly presents as diarrhea but can cause colitis, mimicking inflammatory bowel disease. Our patient is a 78-year-old man on nivolumab therapy for metastatic lung cancer who developed new onset nausea and diarrhea. Endoscopy revealed inflammation of the upper and lower gastrointestinal tract, and histology revealed transmural colon and gastric inflammation. We present a fascinating case of severe concomitant aphthous ulcers, esophagitis, gastritis, and enterocolitis.

Objectives The aim of the study was to review uncommon foreskin dermatopathology conditions clinically and pathologically. Methods A database search of PubMed and Google Scholar were extracted between March 1, 2009, and March 1, 2019, using the search terms "foreskin," "prepuce," "penis," "pathology," "dermatology," and "rare." The search was limited to "humans" and "dermatopathology." Full article texts were reviewed. Reference lists were screened for additional articles. Patient details (diagnosis, dermatopathology, treatment, and follow-up if available) were extracted. We excluded articles written in the non-English language, unusual variants of common conditions, and cases of common dermatologic conditions. Results A list of 369 articles was identified and another screening identified 30 articles for rare foreskin pathologies. Those are divided into categories based on the following etiologies: (a) benign, including congenital (e.g., aposthia), infectious (graft versus host disease and histoplasma), autoimmune (Crohn's disease and pyoderma gangrenosum), and benign neoplasms (neurofibroma, apocrine hidrocystoma, verruciform xanthoma, porokeratosis, penile cutaneous horn, localized amyloidosis) and (b) malignancies, including primary (myeloid sarcoma, basal cell carcinoma, Kaposi's sarcoma, mucosal-associated lymphoid tissue lymphoma), and metastasis. Conclusions We reviewed and discussed unusual benign and malignant dermatopathology conditions that can affect the foreskin.

Synovial sarcoma (SS) is a very rare, aggressive, mesenchymal neoplasm that displays both spindle cell and epithelial histologic characteristics. To our knowledge, there are only 20 documented cases of primary laryngeal SS in the English language literature among all age groups and only three case reports among the pediatric population. Due to its rarity, recognition of this laryngeal neoplasm is often very difficult, and diagnosis relies heavily on immunohistochemistry and its unique translocation between chromosome X and 18 [t(X; 18) (p11.2; q11.2)]. The treatment of SS typically involves a multimodal approach with surgery, chemotherapy, and radiation but despite these options the prognosis remains poor.Here we report the fourth laryngeal SS pediatric patient along with a review of all SS published cases in children. The current report is not only presenting the youngest patient with laryngeal SS but also the pediatric patient with the longest survival.

Introduction Anal squamous cell carcinoma (ASCC) is relatively rare, but its incidence and mortality have been steadily climbing in marginalized populations. We explored the impact of insurance status, education, and income on survival and receipt of chemoradiation therapy. Methods We included patients with ASCC from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2016. Socioeconomic variables included insurance status, level of education, income, and unemployment rate. Cox proportional hazards and multivariate logistic regression were used to determine predictors of survival and receipt of chemoradiation. Results We included a total of 10,868 cases of ASCC. The median age was 55, 10.4 % were black, and 65.4 % were female. Overall, 74.1 % of patients received combination chemoradiation. In multivariate analysis, poorer survival was found for Medicaid (HR 1.52, 95 % CI 1.34−1.74) and uninsured (HR 1.68, 95 % CI 1.35−2.10) patients, and for communities with the lowest rates of high school education (HR 1.17, 95 % CI 1.02−1.38), lowest income (HR 1.29, 95 % CI 1.08−1.54), and highest unemployment (HR 1.21, 95 % CI 1.03−1.40). Patients were less likely to receive combination treatment if they were black (OR 0.76, 95 % CI 0.55−0.92), had Medicaid insurance (OR 0.54, 95 % CI 0.33−0.88) or lower education (OR 0.59, 95 % CI 0.46−0.76). Conclusion Insurance status, level of education, income, and employment impact survival and receipt of treatment in patients with ASCC. Identifying high risk patients and developing targeted interventions to improve access to treatment is integral to reducing these disparities and improving cancer survival.

Multicystic mesotheliomas of peritoneal origin (also termed benign multicystic mesotheliomas) are uncommon and are exceptionally rare in the omentum. Lack of familiarity of this entity could lead to overinterpretation as a malignancy or present a challenge at frozen section. We describe a case of multicystic mesothelioma arising in the omentum found incidentally at laparotomy for endometriosis. Frozen section evaluation presented a challenge. Grossly, the mass in the omentum was multicystic and mucoid, raising the concern for a mucinous neoplasm. The cysts, however, were lined by flattened cells without atypia. At permanent section evaluation, calretinin positivity confirmed the mesothelial origin. Awareness of this entity is important, as it may be interpreted as a malignancy, particularly intraoperatively.

PurposeSodium iodate (NaIO3) has been extensively used as a retinotoxin to induce RPE cell damage and degeneration of photoreceptorsin vitroandin vivo. RIP-Kinase dependent programmed necrosis is an important redundant cell death pathway involved in photoreceptor cell death. We wanted to determine whether these pathways are actively involved in RPE and photoreceptor cell death after NaIO3 insult.MethodsARPE-19 cells were exposed to different concentrations of NaIO3 in the presence or absence of various concentrations of a RIPK inhibitor (Nec-1) or a pan-caspase inhibitor (Z-VAD), individually or combined. Cell death was determined at different time points by MTT (Sigma-Aldrich), LDH (Promega) and TUNEL (Millipore) assay. C57BL/6 and RIP3−/-mice were treated with a peritoneal injection of NaIO3 and eyes were enucleated at day 3 or 7. TUNEL staining was used to evaluate photoreceptor cell death. Photoreceptor cell loss was evaluated by measuring the thickness of outer nuclear layer (ONL). Microglia in the ONL were quantified in a retinal whole mount with Iba-1 antibody. RPE degeneration was also assessed in a RPE whole mount, with ZO-1 antibody.ResultsNaIO3 resulted in significant cell death of ARPE-19 cells. Treatment with Nec-1 resulted in better protection than treatment with Z-VAD (PIn vivoadministration of NaIO3 resulted in significant RPE and photoreceptor destruction with substantial inflammatory cell infiltration. RIP3 knockout animals displayed considerably less RPE and photoreceptor cell loss, as well as drastically less inflammation.ConclusionsProgrammed necrosis is an important cell death pathway mediating NaIO3 RPE and photoreceptor cell toxicity. Blocking the necroptosis pathway may serve as a novel therapeutic strategy for various RPE degenerative diseases.

Objectives Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy with both myelodysplastic and myeloproliferative features. The clinical and pathological features of CMML are highly heterogeneous. It was reported that Hispanic whites had an age-adjusted lower incidence rate of CMML compared to non-Hispanic whites. The aim of this study is to define the cytogenetic and genomic landscape of Hispanic CMML patients and explore their potential clinical significance. Methods Clinically relevant cytogenetic results and 40-gene molecular profiles of Hispanic CMML patients in Puerto Rico (PR) from 2009 to 2018 were obtained retrospectively. Results Total 111 Hispanic CMML patients from PR were diagnosed in our institute from 2009 to 2018. The age range was from 46 to 96 years with a median age of 74. Sixty-five were male and 46 were female. The epidemiological features are similar to that in a general CMML patient population. In total, 107 patients had karyotypes available; 17 patients had abnormal karyotype (17/107, ~16%). Compared with general CMML patients, Hispanic CMML patients had a significantly lower rate of cytogenetic abnormalities (30% vs 16%). Among total 111 Hispanic CMML patients, 40-gene myeloid molecular profiles were performed in 56 CMML patients. Fifty-five out of 56 patients had mutations identified (~98.2%). The most frequent mutated genes were TET2, SRSF2, ASXL1, NRAS, and ZRSR2. Twenty-six of 56 patients (~46.4%) had mutated TET2/wild-type ASXL1. Previous studies indicated that mutated ASXL1, NRAS, RUNX1, and SETBP1 likely associate with an unfavorable prognosis in a general CMML patient population. Mutated TET2 with wild-type ASXL1 (muTET2/wtASXL1) may associate with a favorable prognosis. Compared with general CMML patients, Hispanic CMML patients in this study had relatively lower mutational rates in ASXL1 (30.4% vs 37.0%), NRAS (10.7% vs 11.7%), RUNX1 (5.3% vs 7.9%), and SETBP1 (5.3% vs 8.9%) and a higher rate of muTET2/wtASXL1 (46.4% vs 37.8%). Conclusion Hispanic CMML patients from PR had a significantly lower rate in cytogenetic abnormalities; relatively lower mutational rates in ASXL1, NRAS, RUNX1, and SETBP1; and a higher mutational rate in muTET2/wtASXL1. The findings raise a possibility of a better prognosis in Hispanic CMML patients and could be one of the explanations of a lower incidence rate of CMML in Hispanic population.

A new era of ocular imaging has recently begun with the advent of in vivo confocal microscopy (IVCM), shedding more light on the pathophysiology, diagnosis, and potential treatment strategies for dry eye disease. IVCM is a noninvasive and powerful tool that allows detection of changes in ocular surface epithelium, immune and inflammatory cells, corneal nerves, keratocytes, and meibomian gland structures on a cellular level. Ocular surface structures in dry eye-related conditions have been assessed and alterations have been quantified using IVCM. IVCM may aid in the assessment of dry eye disease prognosis and treatment, as well as lead to improved understanding of the pathophysiological mechanisms in this complex disease. Further, due to visualization of subclinical findings, IVCM may allow detection of disease at much earlier stages and allow stratification of patients for clinical trials. Finally, by providing an objective methodology to monitor treatment efficacy, image-guided therapy may allow the possibility of tailoring treatment based on cellular changes, rather than on clinical changes alone.

Background We investigated sera from elderly subjects with and without age-related macular degeneration (AMD) for presence of autoantibodies (AAbs) against human macular antigens and characterized their identity. Methods Sera were collected from participants in the Age-Related Maculopathy Ancillary (ARMA) Study, a cross-sectional investigation ancillary to the Health ABC Study, enriched with participants from the general population. The resulting sample (mean age: 79.2±3.9 years old) included subjects with early to advanced AMD (n = 131) and controls (n = 231). Sera were tested by Western blots for immunoreactive bands against human donor macular tissue homogenates. Immunoreactive bands were identified and graded, and odds ratios (OR) calculated. Based on these findings, sera were immunoprecipitated, and subjected to 2D gel electrophoresis (GE). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the targets recognized by circulating AAbs seen on 2D-GE, followed by ELISAs with recombinant proteins to confirm LC-MS/MS results, and quantify autoreactivities. Results In AMD, 11 immunoreactive bands were significantly more frequent and 13 were significantly stronger than in controls. Nine of the more frequent bands also showed stronger reactivity. OR estimates ranged between 4.06 and 1.93, and all clearly excluded the null value. Following immunoprecipitation, 2D-GE and LC-MS/MS, five of the possible autoreactivity targets were conclusively identified: two members of the heat shock protein 70 (HSP70) family, HSPA8 and HSPA9; another member of the HSP family, HSPB4, also known as alpha-crystallin A chain (CRYAA); Annexin A5 (ANXA5); and Protein S100-A9, also known as calgranulin B that, when complexed with S100A8, forms calprotectin. ELISA testing with recombinant proteins confirmed, on average, significantly higher reactivities against all targets in AMD samples compared to controls. Conclusions Consistent with other evidence supporting the role of inflammation and the immune system in AMD pathogenesis, AAbs were identified in AMD sera, including early-stage disease. Identified targets may be mechanistically linked to AMD pathogenesis because the identified proteins are implicated in autophagy, immunomodulation, and protection from oxidative stress and apoptosis. In particular, a role in autophagy activation is shared by all five autoantigens, raising the possibility that the detected AAbs may play a role in AMD via autophagy compromise and downstream activation of the inflammasome. Thus, we propose that the detected AAbs provide further insight into AMD pathogenesis and have the potential to contribute to disease biogenesis and progression.