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INTRODUCTION: The expression of androgen receptor (AR) is not commonly tested or studied in uterine cancers, unlike estrogen receptor (ER) and progesterone receptor (PR) which are positive in most endometrial carcinomas. In this series, we evaluated the expression of AR and its comparison to ER and PR in different types of endometrial cancers and have reviewed the literature. MATERIALS AND METHODS: The status of AR, ER, and PR expression were evaluated in 71 cases which were categorized into endometrial endometrioid cancer (EEC), non-endometrioid endometrial cancers (NEEC), and metastatic carcinomas of endometrium. Expression of the receptors were compared to each other as well as to mismatch repair proteins (MMR), p53, and body mass index (BMI) using Fishers Exact test in the StatPlus software. RESULTS: In EECs, the positivity was 97% for all the three receptors. In NEEC, positivity rates were 68%, 48%, and 35% for AR, ER, and PR respectively. In Metastatic carcinomas, AR and ER positivity was seen in 100% while PR was positive in 75% of the cases. In all cancers, the rates were 17% (11/66) for MMR loss, 57% (30/53) for p53 aberrant expression, and 76% (54/71) for the patients with BMI of ≥ 25 (kg/m2). CONCLUSION: AR is expressed in a high percentage of endometrial cancers. Its significance is more evident in high-grade NEEC where ER and PR may not be expressed. These findings warrant further evaluation of AR expression and candidacy of this pathway as a potential therapeutic target in endometrial cancers.

BackgroundThe aim of this study was to determine how Stathmin-1 and Heat Shock Protein 27 (HSP27) can be used as adjunctive biomarkers to differentiate high-grade dysplasia from benign/reactive lesions in cervical tissues. In addition, we aimed to see if any of these markers can differentiate endometrial from endocervical adenocarcinomas.MethodsFifty cases including benign cervical tissue, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ of the endocervix, invasive endocervical adenocarcinoma, and endometrial adenocarcinoma were selected. Stathmin-1 and HSP27 immunohistochemistry (IHC) were performed for each case and the results were compared to the previously available p16 IHC stains.Resultsp16 stained positively in 100% of HSIL, endocervical adenocarcinoma in situ, and invasive endocervical cases. Stathmin-1 stained positively in 43% of HSIL and 90% of endocervical adenocarcinoma in situ and all invasive endocervical cases. Stathmin-1 and p16 were negative in all benign cervical samples. Stathmin-1, HSP27, and p16 stained 100% of LSIL cases. HSP27 stained indiscriminately, including 100% of benign cervical tissue. 87% of the endometrial adenocarcinomas stained positively for p16, Stathmin-1, and HSP27.Conclusionp16 remains superior to both Stathmin-1 and HSP27 in differentiating dysplasia from benign, reactive changes of the cervix.

Individuals diagnosed with colorectal adenomas with high-risk features during screening colonoscopy have increased risk for the development of subsequent adenomas and colorectal cancer. While US guidelines recommend surveillance colonoscopy at 3 years in this high-risk population, surveillance uptake is suboptimal. To inform future interventions to improve surveillance uptake, we sought to assess surveillance rates and identify facilitators of uptake in a large integrated health system. We utilized a cohort of patients with a diagnosis of ≥ 1 tubular adenoma (TA) with high-risk features (TA ≥ 1 cm, TA with villous features, TA with high-grade dysplasia, or ≥ 3 TA of any size) on colonoscopy between 2013 and 2016. Surveillance colonoscopy completion within 3.5 years of diagnosis of an adenoma with high-risk features was our primary outcome. We evaluated surveillance uptake over time and utilized logistic regression to detect factors associated with completion of surveillance colonoscopy. The final cohort was comprised of 405 patients. 172 (42.5%) patients successfully completed surveillance colonoscopy by 3.5 years. Use of a patient reminder (telephone, electronic message, or letter) for due surveillance (adjusted odds = 1.9; 95%CI = 1.2-2.8) and having ≥ 1 gastroenterology (GI) visit after diagnosis of an adenoma with high-risk features (adjusted odds = 2.6; 95%CI = 1.6-4.2) significantly predicted surveillance colonoscopy completion at 3.5 years. For patients diagnosed with adenomas with high-risk features, surveillance colonoscopy uptake is suboptimal and frequently occurs after the 3-year surveillance recommendation. Patient reminders and visitation with GI after index colonoscopy are associated with timely surveillance completion. Our findings highlight potential health system interventions to increase timely surveillance uptake for patients diagnosed with adenomas with high-risk features.

Primary mucosal melanomas of the female genital tract account for one percent or less of all cases of melanoma with even fewer originating in the clitoris. Given the rarity of diagnosis of clitoral melanoma, there is a paucity of data guiding management. There is no supporting evidence that radical vulvectomy (with or without inguinal lymphadenopathy) is associated with improved disease-free or overall survival compared to partial vulvectomy or wide local excision. Additionally, there is no data to evaluate the role of sentinel lymph node biopsy or extensive lymphadenectomy in clitoral melanoma, however previous evidence demonstrates the utility of regional lymph node sampling in predicting survival in women with female genital tract mucosal melanoma. Adjuvant therapy considerations are often extrapolated from their use in treating cutaneous melanomas, including immune checkpoint inhibitors and other immunotherapy agents. Adjuvant radiation therapy has limited utility except in cases of bulky, unresectable disease, or when inguinal lymph nodes are positive for metastasis. The 52 year-old patient presented in this review was diagnosed with locally invasive advanced stage clitoral melanoma presenting as an exophytic clitoral mass. She underwent diagnostic primary tumor resection, which demonstrated ulcerative melanoma with spindle cell features extending to a Breslow depth of at least 28 mm. She subsequently underwent secondary wide local excision with groin sentinel lymph node biopsy, and adjuvant treatment with pembrolizumab. This article also emphasizes the importance of a multidisciplinary team involving gynecologic oncology, medical oncology, radiology, and pathology for management of this rare type of primary mucosal melanoma of the female genital tract.

BackgroundIn recent years, sentinel lymph node excision and ultrastaging have been performed in endometrial carcinomas to obtain information about lymph node status, avoiding unnecessary complete pelvic and paraaortic lymphadenectomy. The purpose of this retrospective study was to provide a comprehensive evaluation of the pathological features of endometrial carcinomas and their significance in association with sentinel lymph node involvement.MethodsPatients with endometrial carcinomas, preceded by sentinel lymph node mapping, were classified into Group-I and Group-II with negative and positive involvement, respectively. The pathological features, associated with sentinel lymph node involvement, were statistically analyzed, including determination of test performance parameters.ResultsAmong 70 patients who had undergone hysterectomy and sentinel lymph node excision, 61 had carcinoma and 9 had atypical hyperplasia. There were 50 patients in Group-I and 10 in Group-II. In Group-II, the significant pathological features were: 1) lower uterine segment involvement (100%), 2) an average tumor size of ≥5 CM, 3) lymphovascular invasion (50%), 4) cervical stromal invasion (40%), and 5) depth of myometrial invasion of ≥50% (50%). The incidences of these pathological features were significantly less in Group-I. Statistical analyses singled out "lower uterine segment involvement" as the most important feature.ConclusionsWe have identified five pathological features which are associated with sentinel lymph node involvement. Since lower uterine segment involvement has occurred in all cases of the Group-II cohort, we recommend FIGO and other organizations that determine staging rules should consider whether tumors that involve the lower uterine segment should be staged as higher than "1a", if the findings in this small series are confirmed by other studies. The results of this study may guide pathologists and oncologists in the diagnostic and therapeutic approaches to management of endometrial carcinomas.

We describe adult-onset Kawasaki disease (KD) and review clinical manifestations and treatment guidelines. Our patient is a 20-year-old female who initially presented to an outside hospital for fever, cervical lymphadenopathy, malaise, exudative tonsillitis, and skin eruption. She received antibiotics for suspected exudative pharyngitis, but experienced continued fevers and presented to the UCLA emergency room one week later. She had diffuse petechial macules coalescing into reticulated patches, fingertip peeling, conjunctival injection, oral erosions, and tongue swelling. Despite her age, given her constellation of symptoms, a diagnosis of typical KD was favored. She was started on high dose aspirin and IVIG, with improvement of rash and conjunctivitis. She was discharged on 325mg of aspirin daily with close follow-up. This case highlights the challenge of diagnosing KD in adults. Although this patient had classic symptoms, she was likely misdiagnosed because KD is rare in adults and without validated criteria. Our patient met the pediatric criteria, suggesting these should be considered when clinical suspicion for adult-onset KD is high. Adult-onset KD is most commonly misdiagnosed as toxic shock syndrome or drug-induced hypersensitivity syndrome and these are important to rule-out. Treatment with high-dose aspirin and IVIG is well established and should be initiated promptly.

Skin reactions related to secukinumab are uncommon. Although the initial phase 3 studies of this medication reported infection and urticaria as adverse cutaneous events, other cases of unique adverse events have since been reported. We are presenting a patient who developed an exuberant hand and foot reaction after starting secukinumab.

Langerhans cell histiocytosis (LCH) is a rare, clinically heterogeneous disease that most commonly occurs in pediatric populations. Congenital self-limited LCH is a benign variant of LCH. It most commonly presents as a diffuse eruption and reports of single lesion cases are infrequent in the literature. Even in the case of congenital self-limited LCH, there is potential for future multisystem relapse, making long-term follow-up important. We present a case of single lesion self-limited LCH in a full-term male infant with interesting morphology. Physical examination revealed a painless, 6 millimeter, well-demarcated, papule encircled by erythema with central hemorrhage. An infectious workup was negative and a punch biopsy was obtained, which showed a dermal infiltrate of histiocytes consistent with a diagnosis of LCH. The lesion healed without intervention within three weeks. Our case highlights the need for dermatologists to consider LCH in the differential diagnosis for lesions of varying morphology in children, as proper identification is necessary to monitor for multisystem recurrence.

Opioids are almost mandatorily used for analgesia for cancer pain and postoperative pain. Opioid analgesics commonly induce nausea as a side effect. However, the genetic factors involved are still mostly unknown. To clarify the genetic background of individual differences in the occurrence of nausea during opioid administration, the incidence of nausea was investigated in 331 patients (Higashi-Sapporo Hospital [HS] group) who received morphine chronically for cancer pain treatment and in 2021 patients (Cancer Institute Hospital [CIH] group) who underwent elective surgery under general anesthesia. We conducted a genome-wide association study of nausea in HS samples. Among the top 20 candidate single-nucleotide polymorphisms (SNPs), we focused on the TMEM132C rs7296262 SNP, which has been reportedly associated with psychiatric disorders. The rs7296262 SNP was significantly associated with nausea in both the HS and CIH groups (TT+TC vs. CC; HS group, p = 0.0001; CIH group, p = 0.0064). The distribution of nausea-prone genotypes for the rs7296262 SNP was reversed between HS and CIH groups. These results suggest that the TMEM132C rs7296262 SNP is significantly associated with nausea during opioid use, and the effect of the SNP genotype on nausea is reversed between chronic and acute phases of opioid use. [ABSTRACT FROM AUTHOR]

As a promising photocatalyst for solar-light driven H2 generation, graphitic carbon nitride (GCN) has been intensively investigated for more than ten years. Herein, highly crystalline Na+-doped GCN (GCN-Na) and NH4Cl-assisted Na+-doped GCN (GCN-Na-NH4Cl) were successfully synthesized. A 25-fold and 65-fold increase in the photocatalytic hydrogen evolution (PHE) rate for GCN-Na and GCN-Na-NH4Cl was achieved compared with pristine GCN under visible light irradiation (λ ≥ 420 nm). Furthermore, the short duration time of the long-lived electron for GCN-Na and GCN-Na-NH4Cl indicated their efficient electron utilization. Apart from the structure and optoelectronic property characterization, femtosecond transient absorption spectroscopy (fs-TAS) was performed to investigate the association between the crystallinity and the PHE performance. The fs-TAS measurements at low excitation density reveal a trap-assisted recombination (tens of picoseconds, ps) of the photogenerated electrons for GCN, GCN-Na and GCN-Na-NH4Cl dispersions, and further suggest that GCN-Na and GCN-Na-NH4Cl possess higher density of shallow-trap sites and their energy level is even closer to the conduction band when compared to that of GCN. Moreover, a strong pump density dependence of the photogenerated electron decay kinetics is observed for GCN-Na and GCN-Na-NH4Cl, indicating a rapid Auger recombination (less than 1 ps) occurring in them under intense illumination. Electrons from the shallower-trap-site as well as electrons from the Auger process would participate in PHE, resulting in a remarkably improved PHE activity for GCN-Na and GCN-Na-NH4Cl. This work not only provides insights into the superior PHE efficiency in highly crystalline GCN but also an NH4Cl-assisted calcination method for the preparation of metal-ion doped GCN with high crystallinity. [ABSTRACT FROM AUTHOR]