Glandular Papilloma Research Articles

Bronchoscopic Interventional Treatment of Mixed Squamous Cell and Glandular Papilloma of Diffuse Trachea: A Case Report and Literature Review

Pulmonary mixed squamous cell and glandular papilloma (MSCGP) is a subtype of pulmonary papilloma, which can be classified as central type and peripheral type based on its site of development. The central type is the most common. The clinical manifestations of pulmonary MSCGP are mainly related to the location of the tumor. Surgery is the main treatment for this disease. Bronchoscopic interventional treatment for the MSCGP in the central trachea could receive satisfactory effect. We reported a patient suffered from diffuse tracheal MSCGP who was treated by bronchoscopic interventional treatment in Respiratory Disease Center, Dongzhimen Hospital of Beijing University of Chinese Medicine, aiming to enhance the recognition of the clinical features and provide clinical references for the diagnosis and treatment of such disease. .

Mixed squamous cell and glandular papilloma of the bronchus

Mixed squamous cell and glandular papilloma of the bronchus

Mucous Gland Adenoma of the Lung: A Neoplastic Counterpart of Mucinous Bronchial Glands

Mucous gland adenoma (MGA) is a rare benign tumor that usually arises in the proximal airway and consists of mucus-secreting cells resembling bronchial glands. Here, we report 2 cases of MGAs and describe their morphologic, immunohistochemical, and molecular profiles in comparison with 19 pulmonary tumors of 5 other histologic types with mucinous cells (invasive mucinous adenocarcinoma, mucoepidermoid carcinoma, mixed squamous cell and glandular papilloma, bronchiolar adenoma/ciliated muconodular papillary tumor, and sialadenoma papilliferum). Two MGAs were found in 1 male patient and 1 female patient, located in the bronchus and trachea, respectively. One MGA was examined by RNA sequencing, and no putative driver mutations (including BRAF, KRAS, and AKT1 mutations) or gene fusions were identified. In another case of MGA, V600E mutations of BRAF and E17K mutations of AKT1 were not detected by allele-specific real-time PCR or digital PCR, respectively. However, a gene expression analysis revealed that the MGA presented a specific RNA expression profile with multiple genes enriched in the salivary gland. The gene expression of NKX3.1 was significantly higher in the MGA case in comparison to normal control lungs (P < .001). We then examined NKX3.1 immunohistochemistry for 2 MGAs and 19 tumors of 5 other histologic types. NKX3.1 was positive in MGA (2/2, 100%), whereas all constituent cells, including mucinous cells, were negative for NKX3.1 in other histologic types (0%, 0/19). In normal lung tissue, NKX3.1 was positive for mucinous acinar cells of the bronchial glands. In conclusion, the gene expression profile, taken together with the histologic similarity between MGA and bronchial glands, and the preferred location of the tumors (proximal airways with submucosal glands) suggest that MGA is a neoplastic counterpart of mucinous bronchial glands. NKX3.1 immunohistochemistry can be a sensitive and specific ancillary marker that distinguishes MGA from other histologic mimics.

Clinicopathological practice in the differential diagnosis of mucoepidermoid carcinoma from neoplasms with mucinous component.

The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific MAML2 gene rearrangement and histological characteristics may be the solution. Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for MAML2 gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs. There were 16 MECs; 62.5% were MAML2 rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were MAML2 rearranged. For the classic and nonclassified MECs without MAML2 rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs (p = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for MAML2 rearrangement. The application of combining MAML2 rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.

872: UNCOMMON PRESENTATION OF A RARE NEOPLASM: AN ENDOBRONCHIAL PAPILLOMA PRESENTING AS SEPSIS

Introduction: Endobronchial papilloma’s (EBP) are rare neoplasms associated with nicotine use and Human Papilloma Virus (HPV). We present a case of a non-smoking, HPV negative male who presented to the hospital with obstructive pneumonia and sepsis due to a lower respiratory tract EBP. Description: A 75-year-old male presented to his primary care doctor with two weeks of dyspnea and productive cough. He was a non-smoker and presented with a medical history of end stage renal disease on hemodialysis, and atrial fibrillation (AF). At his primary care doctor’s office, he was found to be hypoxic and sent to the Emergency Department for further evaluation. Computed tomography-pulmonary angiogram revealed complete atelectasis of his left upper lobe, with consolidation present of the left lower lung. This raised suspicion for an intra-bronchial lesion and pneumonia. Ceftriaxone and azithromycin were initiated, and the patient underwent video fiberoptic white light bronchoscopy. Findings were notable for a lesion completely obstructing the anterior, apical, and posterior segments of the left upper lobe. The lesion was excised, and multiple biopsies were obtained. Pathology revealed glandular papilloma with chronic inflammation. HPV serotyping for 16, 18, 31, 33, and 51 were negative. The patient was kept on a ventilator post-operatively due to hypercapnia and uncontrolled AF. He was extubated less than 24 hours later. He was discharged home with oral cefdinir for 14 days, and 2 L/min of oxygen. He followed up with his pulmonologist one week later in clinic, recovering well, and without complication. Discussion: EBP are benign neoplasms, which represent less than 1% of all lung tumors. Due to their slow growing nature, they primarily present with chronic respiratory symptoms such as exertional dyspnea or cough. This case represents an uncommon presentation of EBP, specifically sepsis. Our patient did not have classic risk factors such as HPV or smoking history. Although rare, clinicians should keep EBP in mind when patients present with sepsis if endobronchial lesions are suspected.

Clinicopathological feature of a resected large mixed squamous cell and glandular papilloma: A case report

Introduction and importanceSolitary endotracheal papilloma is a rare benign lung tumor. It is classified into the following three histological subtypes: squamous cell papilloma (SP), glandular papilloma (GP), and mixed squamous cell and glandular papilloma (MSGP). MSGP is the rarest among them. Herein, we describe a case of a large MSGP.Case presentationA 59-year-old woman underwent computed tomography for the examination of cough, and an 8.2-cm-sized lung mass was noted in the left lingual segment. Bronchoscopy revealed that the left B5 lumen was completely occluded by a tumor. Transbronchial lung biopsy suggested GP; thereafter, a left upper lobectomy was performed. Macroscopic findings showed that the dilated B5 lumen was filled with cauliflower-like tumors. Histopathological findings showed that the majority of the tumors had pseudostratified columnar epithelium, while some had stratified squamous epithelium. The patient was diagnosed with MSGP. Although koilocytosis-like changes, such as perinuclear halo and nuclear deformation, were observed in some portions of the squamous epithelium, immunohistochemical staining was negative for human papillomavirus (HPV).Clinical discussionHPV infection is reportedly associated with SP but not with GP and MSGP. Therefore, MSGP is considered to be caused by squamous metaplasia of a part of GP; this hypothesis is consistent with the present case. However, only one case of MSGP with HPV infection was recently reported, and the etiology and histological features of MSGP remain unclear.ConclusionThere are few reported cases of MSGP, and further case reports are needed to clarify its pathogenesis.

Pulmonary Glandular Papilloma with Abundant Extracellular Mucin and BRAF V600E, AKT1 E17K Mutations: A Case Report

Pulmonary Glandular Papilloma with Abundant Extracellular Mucin and BRAF V600E, AKT1 E17K Mutations: A Case Report

Clinicopathological features of bronchiolar adenoma versus mixed squamous cell and glandular papilloma: a comparative analysis

Objective: To observe the clinicopathological features of bronchiolar adenoma (BA) and mixed squamous cell and glandular papilloma (MSGP). The relationship between them was also analyzed. Methods: Clinical data of eight patients with BA and four patients with MSGP diagnosed in China-Japan Friendship Hospital were collected from January 2018 to January 2020. Hematoxylin-eosin staining and immunohistochemical staining (EnVision method) were used to compare their histopathological characteristics. The hotspots regions of cancer-associated driver genes in lung cancer, using real-time quantitative PCR, were detected in all the cases and the literatures were reviewed. Results: The clinical and imaging manifestations of BA and MSGP were analogous. Histologically they had a two-layer structure including bronchial or bronchiolar-type epithelium and a continuous layer of basal cells,similar to bronchial/bronchiole mucosae. P16 protein was highly expressed in 7/8 of BA and 1/4 of MSGP. Mutations of cancer-associated genes were detected in 4/8 of BA, but none in MSGP. Conclusions: BA and MSGP, derived from different parts of the respiratory tract in the lungs, are rare and benign. Their morphological features overlapped with each other, and some cases are accompanied by genetic changes. It is necessary to pay attention to the differential diagnosis between them and lung adenocarcinoma, especially during the intraoperative diagnosis; and be alert to the potentially malignant components in the tumor or combined cancers.

Sialadenoma Papilliferum of the Bronchus: An Unrecognized Bronchial Counterpart of the Salivary Gland Tumor With Frequent BRAF V600E Mutations.

Sialadenoma papilliferum (SP) is a rare benign tumor of the salivary glands, and only 3 unequivocal cases of SP arising in the bronchus have been reported. We herein describe the histomorphologic and molecular features of 4 bronchial SP cases and discuss the differential diagnosis of this entity and the relationship with its clinicopathologic mimics, in particular, glandular papilloma and mixed squamous cell and glandular papilloma (GP/MP). We encountered 2 male and 2 female patients with bronchial SP (mean: 66.8 y old). All 4 tumors arose in the central bronchus and were characterized by a combination of surface exophytic endobronchial papillary proliferation and a submucosal multicystic component with complex architecture. The neoplastic epithelium consisted predominantly of nonciliated stratified columnar cells with ciliated, squamous, and mucinous cells present focally. While 2 tumors (50%) harbored a BRAF V600E mutation by molecular and immunohistochemical analysis, similar to GP/MP, no KRAS, HRAS, AKT1, or PIK3CA mutations were detected in any of the cases. Two patients were treated with limited resection, while 2 patients underwent lobectomy based on the diagnosis of adenocarcinoma or possible squamous cell carcinoma in situ in the preoperative biopsy. All survived without recurrence or metastasis for 23 to 122 months after treatment. SP can develop in the central bronchus as the bronchial counterpart of the salivary gland tumor and should be considered in the differential diagnosis of endobronchial tumors. In addition, some histologic resemblance and frequent BRAF V600E mutation raise the possibility of SP and GP/MP being on the same disease spectrum.

AKT1 Mutations in Peripheral Bronchiolar Papilloma: Glandular Papilloma and Mixed Squamous Cell and Glandular Papilloma Is Distinct From Bronchiolar Adenoma.

Glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) are rare benign pulmonary tumors occurring in the bronchi. Bronchiolar adenoma (BA) was recently characterized as a pulmonary tumor exhibiting alveolar spread. Both GP/MP and BA are composed of a mixture of glandular, ciliated, squamous, and basal cells. We aimed to clarify whether GP/MP and BA represent the same tumor. We evaluated the detailed histologic characteristics of 11 cases involving pulmonary peripheral tumors that exhibited histologic features of GP/MP or BA, and performed genetic analyses using targeted panel sequencing, allele-specific polymerase chain reaction, and digital polymerase chain reaction. Histologically, 4 and 7 tumors were classified as GP/MP and BA, respectively. GP/MP showed endobronchiolar papillary growth with a pseudostratified or stratified epithelium. In contrast, 5 BAs showed a predominant flat structure with a bilayered or pseudostratified epithelium, whereas 2 BAs showed a GP/MP-like papillary architecture. The mean epithelial thickness in each tumor was significantly larger in GP/MPs and BAs with a GP/MP-like morphology (103 to 242 μm) than in flat-predominant BA (23 to 47 μm, P=0.0010). AKT1 E17K mutations were detected in all GP/MPs and BAs with GP/MP-like morphology but were absent in the 5 flat-predominant BAs. AKT1 mutations were always concurrent with BRAF or HRAS mutations, and the variant allele frequency or percentage of mutant copies of AKT1 mutations was equal to those of BRAF or HRAS mutations. GP/MPs are characterized by AKT1 mutations concurrent with BRAF or HRAS mutations. Peribronchiolar papillary tumors with AKT1 mutations may also be classified as GP/MP.

Pulmonary peripheral glandular papilloma and mixed squamous cell and glandular papilloma frequently harbour the BRAF V600E mutation.

Pulmonary peripheral glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) have very similar histological features to pulmonary ciliated muconodular papillary tumour (CMPT)/bronchiolar adenoma (BA). The underlying genetic relationships between GP/MP and CMPT/BA have rarely been characterised. We aimed to reveal the relationship between them. We performed a clinicopathological review and next-generation sequencing (NGS) study of two GPs and five MPs. Histologically, GPs/MPs showed similar cellular and architectural features to CMPTs/BAs, such as bilayered epithelium, bronchiole-associated lesions and skipping (discontinuous) growth pattern. One MP showed partial and inconspicuous endobronchiolar growth and more glandular structures, which was very similar to the appearance of CMPT/BA. BRAF V600E mutation was detected in four papillomas (57.1%, one GP and three MPs). Overlapping morphological features and comparable mutation profiles support that peripheral GPs/MPs and CMPTs/BAs are on the same disease spectrum. We propose expanding the concept of CMPT/BA and including GP and MP in the CMPT/BA family.

A Case of Solitary Bronchial Glandular Papilloma Resected by Bronchoscopy Using a High-frequency Electrosurgical Snare

A Case of Solitary Bronchial Glandular Papilloma Resected by Bronchoscopy Using a High-frequency Electrosurgical Snare

Clinicopathological analysis of pulmonary mixed squamous cell and glandular papilloma

目的： 探讨肺混合性鳞状细胞和腺性乳头状瘤（PMSGP）的临床、影像及病理学特点，提高多学科共同诊疗质量。 方法： 分析5例PMSGP的临床、影像学表现及病理形态学改变，行免疫组织化学染色和荧光原位杂交（FISH）分子检测，同时结合患者随访资料，深入认识PMSGP的诊断陷阱。 结果： 5例患者均为女性，年龄42~59岁，肿瘤均位于支气管腔内。镜下肿瘤排列成具有纤维血管轴心的复杂分支乳头状结构，由底层的基底样细胞、鳞状细胞及被覆在乳头表面的腺上皮构成。肿瘤细胞异型性较低，核分裂象罕见（病理性核分裂象未见），未见肿瘤性坏死及破坏性浸润。5例均手术完整切除肿块，例1肿瘤细胞发生退变，例2黏液外溢引发炎性反应，周围正常肺泡腔内漂浮脱落的乳头。例3和例4部分肿瘤细胞伴有不典型性，增殖指数增高。前4例患者随访情况良好。例5患者血清学肿瘤标志物及影像学检查均提示恶性肿瘤，行培美曲塞+顺铂方案化疗后，肿块明显缩小，但手术完整切除肿块全部取材仍未见恶性成分。例1，2，5进行FISH检测MAML2基因，均未发现分离信号。 结论： PMSGP是发生在成人的罕见肺良性肿瘤，穿刺活检标本单凭病理形态诊断困难，需要临床多学科协同诊断，建议完整切除肿块，并广泛取材，警惕假浸润现象，避免误诊。.

134 Solitary Pulmonary Mixed Squamous and Glandular Papilloma: A Case Report and Review of Literature

Solitary pulmonary papilloma can be of squamous, glandular or mixed subtype. Mixed squamous and glandular papilloma of the lung is an extremely rare neoplasm, with only 20 cases reported in the literature. Herein we report an unusual case of peripherally located mixed papilloma in a 71-year-old nonsmoking woman. The patient presented with a three-month history of cough. Chest CT scan with contrast revealed a 4.4 x 2.4 x 2.2 cm heterogeneous spiculated left apical mass with possible pleural involvement. PET/CT scan demonstrated high metabolic activity (SUV 17) suggesting malignancy. Several sub-centimeter-sized mediastinal lymph nodes, some with calcifications were also noted. Metastatic work-up was negative. Fine needle aspiration of the mass showed reactive bronchial epithelial cells and a few inflammatory cells. Left upper lobectomy was performed.On gross inspection, a 4.2 x 3.6 cm solid white tan, ill-defined mass was identified with puckering of overlying pleura. Histology showed an expansile tumor, appearing to arise from an endobronchial location with focally infiltrative growth pattern. The tumor was composed of proliferating papillary tufts lined by squamous epithelium and glandular epithelium with overlying columnar ciliated cells. The adjacent lung showed prominent fibrosis due to tumor expansion and growth with interspersed squamous islands. The tumor cells, both the squamous and glandular components, had minimal cytological atypia with no mitosis or necrosis. The overlying pleura and margins were free of tumor. The tumor cells were positive for CK5/6 and p63 while negative for TTF-1, CK7 and Napsin A, CK20, and P16. Reported cases of pulmonary mixed papilloma have male to female ratio of 3:1, with median age of presentation at sixth decade. Vast majority of these cases are centrally located and endobronchial. Surgical resection is considered curative, with only one case of transformation to squamous cell carcinoma reported.

Glandular papilloma of the lung with malignant transformation

Glandular papilloma of the lung with malignant transformation

Peer review report 1 on “Mixed squamous cell and glandular papilloma of the lung resembling early adenocarcinoma: A case report”

Peer review report 1 on “Mixed squamous cell and glandular papilloma of the lung resembling early adenocarcinoma: A case report”

Mixed Squamous Cell and Glandular Papilloma of the Lung in a 64-Year-Old Woman

Mixed squamous cell and glandular papilloma of the lung is an extremely rare benign epithelial tumor showing a mixture of squamous and glandular epithelium. Here, we report a case of mixed squamous cell and glandular papilloma that presented as a solitary nodule in the left lower lobe of a 64-year-old woman. Chest computed tomography demonstrated a lobulated mass in the basal segment of the left lower lobe. The patient underwent a lobectomy under the suspicion of lung malignancy. The histopathological diagnosis was mixed squamous cell and glandular papilloma.

The Unusual Entity of Mixed Squamous and Glandular Papilloma

Mixed squamous and glandular papilloma of the lung is uncommon. Current literature demonstrates that there are less than 20 cases documented worldwide, though likely underreported. We present a case of a 58 y.o. female with history of COPD who was found to have mixed squamous and glandular papilloma, confirmed by histology. This case highlights an unusual etiology of endobronchial lesion that can mimic a malignancy. Clinicians should be aware of this entity because resection can be curative and prognosis is good.

A Solitary Mixed Squamous Cell and Glandular Papilloma of the Lung

Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is exceedingly rare, with only 18 cases reported in the literature. Herein, we report a case of mixed papilloma and its associated immunohistochemical and positron emission tomographic (PET) findings. A 60-year-old Japanese male with a smoking history of 40 pack-years presented with a smooth-edged pulmonary lesion in the right S5 segment on computed tomography (CT). F18-fluorodeoxyglucose (FDG) PET revealed abnormally increased FDG uptake in the mass (maximum standardized uptake value, 3.4). We performed right middle lobectomy and combined partial resection of the S8 segment. The 1.8-cm tumor that filled the enlarged lumen of the B5b was histologically diagnosed as mixed papilloma. Immunohistochemically, the pseudostratified columnar epithelium was positive for cytokeratin (CK) 5/6 and CK7. p40 positivity was predominant in the basal and squamous cells. Thyroid transcription factor-1 and carcinoembryonic antigen were negative on immunostaining. Malignant features were absent. The postoperative course has been uneventful for 3 months after the surgery. No recurrences were reported after the surgical resection of the mixed papilloma. Therefore, surgical resection may be considered the mainstay of curative treatment.

肺野末梢に発生し，肺癌の臨床像を呈した扁平上皮腺上皮性混合型乳頭腫の1例

肺野末梢に発生し，肺癌の臨床像を呈した扁平上皮腺上皮性混合型乳頭腫の1例