A combination of radiomic features, clinic characteristics, and serum tumor biomarkers to predict the possibility of the micropapillary/solid component of lung adenocarcinoma.

BACKGROUND: Invasive lung adenocarcinoma with MPP/SOL components has a poor prognosis and often shows a tendency to recurrence and metastasis. This poor prognosis may require adjustment of treatment strategies. Preoperative identification is essential for decision-making for subsequent treatment. OBJECTIVE: This study aimed to preoperatively predict the probability of MPP/SOL components in lung adenocarcinomas by a comprehensive model that includes radiomics features, clinical characteristics, and serum tumor biomarkers. DESIGN: A retrospective case control, diagnostic accuracy study. METHODS: This study retrospectively recruited 273 patients (males: females, 130: 143; mean age ± standard deviation, 63.29 ± 10.03 years; range 21-83 years) who underwent resection of invasive lung adenocarcinoma. Sixty-one patients (22.3%) were diagnosed with lung adenocarcinoma with MPP/SOL components. Radiomic features were extracted from CT before surgery. Clinical, radiomic, and combined models were developed using the logistic regression algorithm. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC). Studies were scored according to the Radiomics Quality Score and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines. RESULTS: The radiomics model achieved the best AUC values of 0.858 and 0.822 in the training and test cohort, respectively. Tumor size (T_size), solid tumor size (ST_size), consolidation-to-tumor ratio (CTR), years of smoking, CYFRA 21-1, and squamous cell carcinoma antigen were used to construct the clinical model. The clinical model achieved AUC values of 0.741 and 0.705 in the training and test cohort, respectively. The nomogram showed higher AUCs of 0.894 and 0.843 in the training and test cohort, respectively. CONCLUSION: This study has developed and validated a combined nomogram, a visual tool that integrates CT radiomics features with clinical indicators and serum tumor biomarkers. This innovative model facilitates the differentiation of micropapillary or solid components within lung adenocarcinoma and achieves a higher AUC, indicating superior predictive accuracy.

A new tool to predict aggressive lung cancer types before surgeryWe developed a tool to help doctors determine whether lung cancer is one of the more dangerous types, called micropapillary (MPP) or solid (SOL) patterns, before surgery. These patterns can be more harmful and spread quickly, so knowing they are there can help doctors plan the best treatment. We looked at the cases of 273 lung cancer patients who had surgery and found that 61 of them had these aggressive cancer types. To predict these patterns, we used a computer process known as logistic regression, analyzing CT scan details, health information, and blood tests for cancer markers. Based on CT scans, our tool was very good at predicting whether these patterns were present in two patient groups. However, predictions using only basic health information like the size of the tumor and whether the patient smoked needed to be more accurate. We found a way to make our predictions even better. Combining all information into one chart, known as a nomogram, significantly improved our ability to predict these dangerous cancer patterns. This combined chart could be a big help for doctors. It gives them a clearer picture of the cancer's aggressiveness before surgery, which can guide them to choose the best treatment options. This approach aims to offer a better understanding of the tumor, leading to more tailored and effective treatments for patients facing lung cancer.

[Clinicopathological features of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma].

Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.

Invasive Papillary Adenocarcinoma of Gallbladder: A Case Report.

Papillary gallbladder adenocarcinoma (PGA) represents 5.0% of all malignant tumor of gallbladder. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis, often proving fatal. A 63 year old female presented with right upper quadrant pain, palpable gallbladder on clinical examination and hypoechoic shadow suggestive of gall stone inside on ultrasound. But during an attempt to open cholecystectomy surgeons found tiny papillary growth involving whole fundus and part of the body on June 2020 at an outside hospital, Khulna, Bangladesh. Radical cholecystectomy was done by the surgeon with enlarged portal lymph node dissection and a small portion of hepatic resection. Histopathology demonstrated a well-differentiated invasive papillary adenocarcinoma with muscle invasion. There was no metastasis in the liver and lymph nodes show reactive hyperplasia.

[A Case of Intraductal Papillary Mucinous Adenocarcinoma with Hepatic Dysfunction Due to Tumor Perforation into the Bile Duct].

A 58-year-old woman presented with a complaint of weight loss. Abdominal computed tomography showed dilatation of the biliary and pancreatic ducts and a mural nodule in the pancreatic duct. The diagnosis was intraductal papillary mucinous neoplasm(IPMN). Endoscopic retrograde cholangiopancreatography(ERCP)and cholangioscopy revealed a fistula between the common bile duct and the IPMN. A sudden increase in hepatobiliary enzymes was noted preoperatively. ERCP showed that the common bile duct was obstructed by mucus. A nasobiliary drainage tube was inserted into the bile duct endoscopically and kept open by daily tube washing, and the liver dysfunction improved. Total pancreatectomy, splenectomy, and regional lymph node dissection were performed. Histological examination confirmed that the primary tumor was mixed invasive intraductal papillary mucinous adenocarcinoma. The patient remains alive and well with no evidence of recurrence 18 months after resection.

Value of Immunohistochemistry to Differentiate Digital Papillary Adenocarcinoma From Acral Hidradenoma With Papillary Structures.

ABSTRACT: Digital papillary adenocarcinoma is a malignant adnexal tumor with a predilection for acral sites. Hidradenoma is a benign solid and cystic sweat gland neoplasm with focal ductal and glandular differentiation and good outcomes. Hidradenomas can occur at acral sites and show papillary structures; for this reason, they are included in the differential diagnosis of digital papillary adenocarcinoma, and immunohistochemistry is a valuable tool in this scenario. We described a case of a 43-year-old man with an epithelial tumor showing papillary structures in the intermediate phalanx of the fourth finger. There was diffuse positivity for p63 and negativity for S100 protein, suggesting that this tumor was an acral hidradenoma with papillary structures.

Immunohistochemical features of canine ovarian papillary adenocarcinoma and utility of cell block technique for detecting neoplastic cells in body cavity effusions.

Dogs with ovarian papillary adenocarcinoma occasionally present with ascites and/or pleural effusion. These aspirated fluids often contain a large number of cells, and distinction between neoplastic cells and activated mesothelial cells can be difficult. In this study, 7 cases of canine ovarian papillary adenocarcinoma, including 3 with ascites and pleural effusion, were immunohistochemically examined. Ovarian tumor cells were positive for cytokeratin CAM5.2 (CAM5.2), Wilms' tumor 1 (WT-1) and progesterone receptor (PR) in all 7 cases. A metastatic lesion of the mediastinum in one case was also positive for CAM5.2, WT-1 and PR. Immunohistochemistry on cell blocks obtained from ascites and/or pleural effusion of 2 cases revealed the presence of PR-positive epithelial cells. Whereas, activated mesothelial cells in ascites or pleural effusion collected from dogs without neoplastic lesions were negative for PR. In addition, surface epithelium and subsurface epithelial structures (SES) of normal canine ovaries, that are considered to be the cell of origin for ovarian papillary adenocarcinoma, were also positive for CAM5.2, WT-1 and PR. These results indicate that, together with CAM5.2, WT-1 and PR is a useful diagnostic marker for canine ovarian papillary adenocarcinoma. Expression of PR may be associated with progesterone-dependent nature of canine ovarian papillary adenocarcinoma.

Wide Local Excision with Sentinel Lymph Node Biopsy for Digital Papillary Adenocarcinoma: A Case Report.

Digital papillary adenocarcinoma (DPA) is a rare but locally aggressive eccrine tumour that has metastatic potential and most frequently found in the upper extremity. It usually presents as an unremarkable swelling of the skin, commonly misdiagnosed as a benign lesion. We present a 67-year-old male who presented with a slowly growing mass of the right middle finger that was biopsied and diagnosed with DPA. The patient was treated with wide local excision (WLE) and sentinel lymph node biopsy by us during the same operative encounter. This report highlights the need for increased clinical vigilance to diagnose DPAs, and that WLE and sentinel lymph node biopsies can be safe and effective treatments offered. Level of Evidence: Level V (Therapeutic).

Elastin in pulmonary pathology: relevance in tumours with a lepidic or papillary appearance. A comprehensive understanding from a morphological viewpoint.

Elastin and collagen are the main components of the lung connective tissue network, and together provide the lung with elasticity and tensile strength. In pulmonary pathology, elastin staining is used to variable extents in different countries. These uses include evaluation of the pleura in staging, and the distinction of invasion from collapse of alveoli after surgery (iatrogenic collapse). In the latter, elastin staining is used to highlight distorted but pre-existing alveolar architecture from true invasion. In addition to variable levels of use and experience, the interpretation of elastin staining in some adenocarcinomas leads to interpretative differences between collapsed lepidic patterns and true papillary patterns. This review aims to summarise the existing data on the use of elastin staining in pulmonary pathology, on the basis of literature data and morphological characteristics. The effect of iatrogenic collapse and the interpretation of elastin staining in pulmonary adenocarcinomas is discussed in detail, especially for the distinction between lepidic patterns and papillary carcinoma.

Primary nasopharyngeal papillary adenocarcinoma: A CARE-compliant case report.

RATIONALE: Primary nasopharyngeal papillary adenocarcinoma is a rare nasopharyngeal neoplasm with a good prognosis and a low propensity for regional recurrence. To date, only few cases of primary nasopharyngeal papillary adenocarcinoma have been reported in the literature. PATIENT CONCERNS: A 24-year-old female patient presented with intermittent hemoptysis and blood tinge nasal discharge. DIAGNOSIS: An exophytic and pedunculated mass over the roof of the nasopharynx was found on nasopharyngoscope. Biopsy was done and the pathology confirmed well-differentiated primary nasopharyngeal papillary adenocarcinoma, strongly positive for CK7, and transcription termination factor 1; but negative for thyroglobulin. The final diagnosis was primary nasopharyngeal papillary adenocarcinoma, well-differentiated, pT1N0M0, stage I. INTERVENTIONS: The patient underwent excision of nasopharyngeal tumor under sinuscopic assistance. OUTCOMES: : No local recurrence or distant metastasis was noted during the 6 months of follow-up. LESSONS: We aim at highlighting the importance of a thorough differential diagnosis of nasopharyngeal tumor. Further investigation is still needed for providing evidence to standardize the treatment protocol.

Repeat Fine Needle Aspiration Cytology Refines the Selection of Thyroid Nodules for Afirma Gene Expression Classifier Testing.

Background: Molecular testing (MT) refines risk stratification for thyroid nodules that are indeterminate for cancer by fine needle aspiration (FNA) cytology. Criteria for selecting nodules for MT vary and remain largely untested, raising questions about the best strategy for maximizing the usefulness of MT while minimizing the harms of overtesting. We used a unique data set to examine the effects of repeat FNA cytology-based criteria for MT on management decisions and nodule outcomes. Methods: This was a study of adults (age 25-90 years; 281 women and 72 men) with cytologically indeterminate (Bethesda III/IV) thyroid nodules who underwent repeat FNA biopsy and Afirma Gene Expression Classifier (GEC) testing (N = 363 nodules from 353 patients) between June 2013 and October 2017 at a single institution, with follow-up data collected until December 2019. Subgroup analysis was performed based on classification of repeat FNA cytology. Outcomes of GEC testing, clinical/sonographic surveillance of unresected nodules, and histopathologic diagnoses of thyroidectomies were compared between three testing approaches: (i) Reflex (MT sent on the basis of the initial Bethesda III/IV FNA), (ii) SemiRestrictive (MT sent if repeat FNA is Bethesda I-IV), and (iii) Restrictive (MT sent only if repeat FNA is Bethesda III/IV) testing approaches. Results: Restricting MT to nodules that remain Bethesda III/IV on repeat FNA would have missed 4 low-risk cancers and 3 noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) (collectively 2% of the test population) but would have avoided diagnostic surgery for 42 benign nodules (12% of the test population). The Restrictive testing strategy was more specific (delta 0.126 confidence interval [CI 0.093 to 0.159] and 0.129 [CI 0.097 to 0.161], respectively) but less sensitive (delta -0.339 [CI -0.424 to -0.253] and -0.340 [CI -0.425 to -0.255], respectively) than the Reflex and SemiRestrictive approaches for detecting NIFTP or cancer. Conclusions: Repeat FNA cytology can guide the selection of cytologically indeterminate thyroid nodules that warrant MT. The Restrictive model of performing Afirma GEC only on nodules with two separate biopsies showing Bethesda III/IV cytology would reduce the rate of diagnostic surgery for histologically benign nodules while missing only rare low-risk tumors. Given the low but nontrivial risks of thyroidectomy, the higher specificity of the Restrictive testing approach disproportionately outweighs the potential harms.

Pathological characterization of intracholecystic papillary neoplasm: A recently proposed preinvasive neoplasm of gallbladder.

Intracholecystic papillary neoplasm (ICPN) is a recently proposed gallbladder neoplasm. Its prevalence and pathologies remain to be clarified. A total of 38 ICPN cases (28 ICPNs identified among 1904 cholecystectomies (1.5%) and in 100 surgically resected primary gallbladder neoplasms (28%) in Fukui Prefecture Saiseikai Hospital, Japan, and other 10 ICPNs) were examined pathologically and immunohistochemically. They were composed of 21 males and 17 females with a mean age of 75 years old, and presented intraluminal growth of papillary lesions with fine fibrovascular stalks. ICPNs were relatively frequent in the fundus (n = 11) and body (n = 9). Grossly, the conglomerated sessile type (n = 30) was more frequent than the isolated polypoid type (n = 8). All cases were classified as high-grade dysplasia, and they were further divided into 22 cases presenting irregular structures and 16 cases presenting regular structures. The former showed frequent complicated lesions and stromal invasion (54.5%) compared to the latter (12.5%). Twenty-four cases showed predominantly either of four subtypes (11 gastric, 7 intestinal, 4 biliary and 2 oncocytic subtype), while the remaining14 cases showed mixture of more than two subtypes. In conclusion, ICPN presented unique preinvasive neoplasm with characteristic histopathologies. Irregular histologies and complicated lesions of ICPN were related to stromal invasion.

Papillary Neoplasms of the Salivary Duct System: A Review.

Papillary lesions of the salivary duct systems are uncommon. They encompass a heterogeneous group of benign, intermediate, and potentially aggressive neoplasms. With a few exceptions, historical descriptive terms such as papillary adenocarcinoma, papillary cystadenocarcinoma, and papillary adenoma are being replaced by defined entities, at same time acknowledging the papillary features as a histologic pattern. The evolving genetic landscape of these lesions increasingly permits their reproducible categorization. This article discusses those papillary proliferations encountered in the salivary glands with a focus on intraductal papillary mucinous neoplasms and cystadenomas. Intraductal carcinomas and sialadenoma papilliferum are addressed in separate articles in this issue.

Preoperative diagnosis of intraductal papillary neoplasm of the bile duct with endoscopic ultrasound.

Intraductal papillary mucinous neoplasm of the bile duct is a rare tumour only recently classified as a distinct pathological entity. These neoplasms, rarely encountered in clinical practice in the UK, are now considered to be important precursors for the development of cholangiocarcinoma. We present a histologically confirmed case of intraductal papillary neoplasm of the bile duct in a male patient and discuss the main radiographic manifestations of this rare condition across multiple imaging modalities, with an emphasis on the imaging features of endoscopic ultrasonography and its role in establishing the diagnosis.

Malignant Ciliated Muconodular Papillary Tumors of the Lung: A Case Report.

Ciliated muconodular papillary tumors (CMPTs) are rare peripheral lung lesions, characterized by papillary architecture and ciliated columnar cells admixed with mucous cells and basal cells. Only about 50 cases have been reported to date and is categorized as a benign neoplasm. In this article, we report an extremely rare case of 79-year-old man with a CMPT that developed in his right upper lobe. The central region of the tumor showed features of classic CMPT, while marginal area of the tumor showed the characteristics of invasive lung cancer. In central classic CMPT region, the ciliated, basal, and mucous cells were positive for thyroid transcription factor-1, cytokeratin 7 (CK7), and NapsinA. Basal cells were positive for CK5/6 and p40. Mucous cells were weakly positive for MUC2 and MUC5AC. However, CK5/6 and p40 were negative in the peripheral malignant area. Both of the benign and malignant regions had an EGFR driver mutation in exon 21. We concluded that this tumor was an extremely rare malignant case of CMPT.

Papillary-cystic neoplasms of the middle ear are distinct from endolymphatic sac tumours.

AIMS: Papillary neoplasms of the middle and inner ear are rare and poorly characterised. The current World Health Organization classification divides them into two major subtypes: aggressive papillary tumours (APTs) and endolymphatic sac tumours (ELSTs). The aim of this article is to present two papillary neoplasms of the middle ear that do not fit into either the classic APT category or the classic ELST category, and compare them with three ELSTs. METHODS AND RESULTS: The patients were a 48-year-old female and a 59-year-old male without a history of other neoplasms. Histology showed papillary-cystic growth of predominantly oncocytic (Case 1) or mucinous (Case 2) cells surrounded by a p63-positive basal layer. The overall histology was reminiscent of oncocytic sinonasal papilloma (Case 1) and pancreatobiliary or salivary intraductal papillary mucinous neoplasms (Case 2). Ovarian-type stroma, invasion and malignant features were absent. Immunohistochemistry revealed expression of cytokeratin (CK) 7, but not carbonic anhydrase IX (CAIX) or paired box gene 8 (PAX8) (except for very focal PAX8 expression in Case 1). The TST15 gene panel and HRAS sequencing revealed no pathogenic mutations in BRAF, KRAS, EGFR, AKT1, or HRAS. The TruSight RNA fusion panel revealed an MKRN1-BRAF fusion in Case 1. No fusion was detected in Case 2. The three ELSTs showed classic features of the entity, expressed CK7, epithelial membrane antigen, PAX8, and CAIX, and lacked a basal cell layer. CONCLUSION: These novel cases suggest that papillary tumours of the ear represent a heterogeneous spectrum of distinct neoplasms unified by a prominent papillary-cystic pattern rather than a single entity. Future studies should clarify whether the MKRN1-BRAF fusion is a defining recurrent driver event, especially in those cases reported as sinonasal-type middle ear papillomas.