Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients\' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.
呼吸道乳头状瘤是呼吸道较常见的良性肿瘤，少数可发生恶变。该病起病隐匿，缺乏特异性临床表现，其表现与肿瘤生长方式、部位、大小密切相关，可有喉、气管、支气管、肺实质等多个部位受累，引起咳嗽、声音嘶哑、发音困难，严重者可致呼吸道梗阻。目前，呼吸道乳头状瘤的治疗缺乏规范统一的标准，且尚无治愈该病的有效方法，手术是减轻患者症状、预防气道梗阻的主要治疗方式。然而呼吸道乳头状瘤复发率高，患者往往需要经历多次手术治疗，频繁的手术降低患者的生活质量，增加患者的疾病负担与经济负担。贝伐珠单抗作为血管内皮生长因子结合抗体抑制剂，是一种有希望的辅助治疗方式，在减轻症状、减少手术频率方面表现出较好的潜力。本文主要对贝伐珠单抗治疗呼吸道乳头状瘤的有效性及安全性进行综述，并探讨全身性应用和病灶内注射贝伐珠单抗治疗呼吸道乳头状瘤的差异及疗效。.

Squamous papilloma is a benign neoplasm that originates from the stratified squamous epithelium of the mucous membrane. Its principal etiological factor is human papillomavirus infection, with a predilection for manifesting within the oral cavity. Squamous papilloma predominantly affects regions on the palate, cheeks, lips and tongue. However, to the best of our knowledge, the occurrence of squamous papilloma within the confines of the mandible remains unreported hitherto. The present report documents a case of squamous papilloma involving the mandible who was managed at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) in January 2023. The patient underwent a series of recurrent jaw inflammations, manifesting with malignant imaging characteristics. Subsequent pathological analysis confirmed a diagnosis of papilloma in the jaw. The present report highlights the pivotal role of prolonged inflammation in the genesis of jaw squamous papilloma, prompting avenues for further investigation, including the potential of inflammation to induce aberrant cell growth, mediate cell interactions, orchestrate cytokine actions and influence stress mediators. In addition, the current study posits a plausible connection between persistent inflammation, compromised epithelial integrity and an increased likelihood of head and neck papilloma, particularly concerning human papillomavirus infection. This article delineates the clinical attributes of the uncommon manifestations of jaw papilloma and delves into the associated mechanisms, thereby contributing to an enhanced comprehension of jaw disorders. This comprehensive insight equips clinicians with a heightened knowledge base for more precise diagnosis and treatment of analogous cases.

BACKGROUND: With advancements in medicine and economy, it would be expected that there will be changes in the clinical characteristics of upper respiratory papillomatosis. The aim of this study was to examine the current clinical characteristics of upper respiratory papillomatosis, as there are no recent data in the literature.
METHODS: The medical records of 1894 patients with upper respiratory papillomatosis were retrospectively reviewed. Data extracted included clinical features, laryngoscopy images, and surgical procedure data.
RESULTS: The upper frequency of upper respiratory papillomatosis in the oropharynx was 69.1 %, and in the larynx was held 28.9 %. The overall postoperative relapse rate was 2.4 %. The relapse rate of laryngeal papillomatosis was 6.5 %. Approximately 2.6 % of cases were in children. All postoperative recurrences in children were laryngeal, and the recurrence rate was 30.4 %.
CONCLUSIONS: The oropharynx has the highest frequency of upper respiratory papillomatosis. The larynx, however, has the highest rate of postoperative recurrence. Compared to adults, children are more likely to experience a postoperative recurrence.

UNASSIGNED: Solitary mixed squamous cell and glandular papilloma of the lung is an extremely rare benign neoplasm. We describe FDG PET/CT findings in a case of solitary mixed squamous cell and glandular papilloma of the lung with high serum carcinoembryonic antigen level (63.3 ng/mL; reference, <5 ng/mL). The tumor showed intense FDG uptake with SUVmax of 23.8 mimicking lung cancer.

BACKGROUND: This article presents a challenging case involving an elderly male patient with a misdiagnosed intraductal mammary papilloma initially identified as a sweat adenoma through ultrasound imaging. The study aims to explore the histopathology, clinical presentations, and sonographic features of both conditions, emphasizing the contributing factors to the diagnostic misstep.
METHODS: A 61-year-old male reported a persistent left breast mass, along with pain and swelling, spanning a 6-month duration.
METHODS: Ultrasound examination indicated a deep, square, mixed-echo mass in the left nipple, initially suggestive of a sweat adenoma. However, subsequent pathological analysis following resection under general anesthesia confirmed an intraductal papilloma.
METHODS: The patient underwent surgical resection of the left breast mass under general anesthesia.
RESULTS: Post-surgery, the patient exhibited satisfactory recovery; however, regrettably, he was lost to follow-up.
CONCLUSIONS: This study underscores the challenge in differentiating between clear cell sweat adenoma and male intraductal mammary papilloma solely based on ultrasonic characteristics. It emphasizes the susceptibility of ultrasound-based diagnoses to misinterpretation, highlighting the critical need for a comprehensive pathological examination to establish a definitive diagnosis.

Rat model of N-nitrosomethylbenzylamine (NMBzA)-induced esophageal squamous cell carcinoma (ESCC) is routinely used to study ESCC initiation, progression and new therapeutic strategies. However, the model is time-consuming and malignant tumor incidences are low. Here, we report the usage of multi-kinase inhibitor sorafenib as a tumor promoter to establish an efficient two-stage NMBzA-induced rat ESCC carcinogenesis model, resulting in increments of tumor incidences and shortened tumor formation times. By establishing the model and applying whole-genome sequencing, we discover that benign papillomas and malignant ESCCs harbor most of the \"driver\" events found in rat ESCCs (e.g. recurrent mutations in Ras family, the Hippo and Notch pathways and histone modifier genes) and the mutational landscapes of rat and human ESCCs overlap extensively. We generate tumor cell lines derived from NMBzA-induced papillomas and ESCCs, showing that papilloma cells retain more characteristics of normal epithelial cells than carcinoma cells, especially their exhibitions of normal rat cell karyotypes and inabilities of forming tumors in immunodeficient mice. Three-dimensional (3-D) organoid cultures and single cell RNA sequencing (scRNA-seq) indicate that, when compared to control- and papilloma-organoids, ESCC-organoids display salient abnormalities at tissue and single-cell levels. Multi-omic analyses indicate that NMBzA-induced rat ESCCs are accompanied by progressive hyperactivations of the FAT-Hippo-YAP1 axis and siRNA or inhibitors of YAP1 block the growth of rat ESCCs. Taken together, these studies provide a framework of using an effective rat ESCC model to investigate multilevel functional genomics of ESCC carcinogenesis, which justify targeting YAP1 as a therapeutic strategy for ESCC.

暂无摘要。

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People\'s Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.
目的： 探讨端粒酶逆转录酶（TERT）启动子在膀胱内翻性尿路上皮病变中的突变情况及其在鉴别诊断中的意义。 方法： 收集2016年3月至2022年2月青岛市城阳区人民医院32例及青岛大学附属医院24例病理科诊断为膀胱内翻性尿路上皮病变56例，包括7例旺炽性腺性膀胱炎、13例内翻性尿路上皮乳头状瘤、8例内翻性低度恶性潜能的尿路上皮肿瘤、17例低级别非浸润性内翻性尿路上皮癌、5例高级别非浸润性内翻性尿路上皮癌及6例巢状亚型尿路上皮癌，总结其临床资料及组织病理学特征，并通过一代测序分析TERT启动子突变情况。 结果： 旺炽性腺性膀胱炎和内翻性尿路上皮乳头状瘤中均未发现有TERT启动子突变，TERT启动子在内翻性低度恶性潜能的尿路上皮肿瘤、低级别和高级别非浸润性内翻性尿路上皮癌以及巢状亚型尿路上皮癌中的突变比例分别为1/8、8/17、2/5和6/6。TERT启动子突变比例在内翻性低度恶性潜能的尿路上皮肿瘤、低级别以及高级别非浸润性内翻性尿路上皮癌之间差异均无统计学意义（P>0.05）。巢状亚型尿路上皮癌中6例全部突变，与内翻性低度恶性潜能的尿路上皮肿瘤和非浸润性内翻性尿路上皮癌突变比例相比，差异有统计学意义（P<0.05）。突变形式上，TERT启动子突变13/17为C228T，4/17为C250T。 结论： 形态学结合TERT启动子突变检测有助于对膀胱非浸润性内翻性尿路上皮病变的鉴别诊断。.

BACKGROUND: Twenty to thirty percent of patients taking BRAF inhibitors such as vemurafenib (PLX4032) for melanoma develop cutaneous squamous cell carcinomas.
OBJECTIVE: This study aimed to elucidate the chemopreventive effect of essential oil from Mentha aquatica L. cv. Lime (EO) and its major constituents, limonene and carvone (L + C) that made up 45.68% of the EO, against PLX4032-induced cutaneous side effects.
METHODS: PLX4032 accelerated skin papilloma formation and keratinocyte HRAS mutation in 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced two-stage skin carcinogenesis mouse model was used to evaluate the in vivo bioefficacy of EO and L + C. The effects and molecular mechanisms of EO and L + C on deregulating mouse PDVHRASQ61L keratinocyte activities were demonstrated using a spectrum of bioactivity assays, western blotting, immunochemistry, and keratinocyte-macrophage co-culture assay.
RESULTS: Treatment with EO suppressed colony formation ability, cell migration, invasion, and induced G2/M cell-cycle arrest and apoptosis in PDVHRASQ61L keratinocytes, and L + C treatment inhibited colony formation, cell migration and invasion of PDV cells. In mouse skin irritated with DMBA/TPA (DT group) or DMBA/TPA with PLX4032 (DTP group), topical application of EO and L + C significantly delayed papilloma appearance and reduced papilloma incidence compared to DT or DTP controls. Histopathology results showed that EO and L + C treatment attenuated K14+ keratinocyte proliferation and paradoxical MAPK activation, and shifted the macrophage population from M2 (CD163+) to M1 (iNOS+) in the mouse skin microenvironment. The conditioned medium of EO or L + C pre-treated PDV keratinocytes promoted M0 macrophages to differentiate from THP-1 cells into M1-like macrophages.
CONCLUSIONS: This study demonstrates that EO and L + C in combination prevent PLX4032-induced cutaneous side-effects and skin carcinogenesis in mice through reprogramming the macrophage cell population and inhibiting keratinocyte activity. Both mint EO and the natural products L + C can be considered to be effective chemopreventive agents that might be useful in reducing cutaneous lesions in human patients administrated with BRAF inhibitors.