Mesonephric-type adenocarcinomas of the ovary: prevalence, diagnostic reproducibility, outcome, and value of PAX2.

Mesonephric-type (or -like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four-marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four-marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376-0.727) with the integration of the four-marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first-line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62-5.85; p < 0.0001) compared with patients with EC, when adjusted for age, stage, and p53 status. A diagnosis of MA has prognostic implications for stage I disease, and due to the subtlety of morphological features in some tumors, a low threshold for ancillary testing is recommended.

Feline lung-digit syndrome: A differential diagnosis for shifting, waxing and waning lameness in a cat.

The clinical presentation, cytologic findings, radiographic findings, and postmortem assessment of a cat with primary pulmonary adenocarcinoma with multiple digital metastasis are described. An unusual shifting, waxing and waning pattern of lameness, suspected to be an early manifestation of digital metastasis before any gross lesions were visible, was documented. Initial cytologic finding of a lung nodule was equivocal for diagnosis of neoplasia despite being strongly suspicious. Palliative management was short-lived, with rapid progression culminating in widespread metastasis to multiple digits, muscles, and other organs. The diagnosis of pulmonary adenocarcinoma was confirmed via necropsy and histopathology. Key clinical message: This case report highlights that feline lung-digit syndrome is an important differential diagnosis for an acute, waxing and waning, shifting leg lameness in an older cat. This pattern of lameness should raise the index of suspicion for an underlying primary lung neoplasm, and thoracic imaging (radiographs) should be considered.

Syndrome pulmonaire-digital félin : un diagnostic différentiel des boiteries changeantes, croissantes et décroissantes chez un chatLa présentation clinique, les résultats cytologiques, les résultats radiographiques et l'évaluation post mortem d'un chat atteint d'adénocarcinome pulmonaire primaire avec métastases numériques multiples sont décrits. Un schéma inhabituel de boiterie, variable, croissante et décroissante, suspecté d'être une manifestation précoce de métastases digitales avant que des lésions macroscopiques ne soient visibles, a été documenté. La découverte cytologique initiale d'un nodule pulmonaire était équivoque pour le diagnostic de néoplasie bien qu'elle soit fortement suspecte. La prise en charge palliative a été de courte durée, avec une progression rapide aboutissant à des métastases généralisées à plusieurs doigts, muscles et autres organes. Le diagnostic d'adénocarcinome pulmonaire a été confirmé par autopsie et histopathologie.Message clinique clé :Ce rapport de cas souligne que le syndrome pulmonaire-digital félin est un diagnostic différentiel important pour une boiterie aiguë, croissante et décroissante et mobile des pattes chez un chat ágé. Ce type de boiterie devrait faire suspecter une tumeur primaire du poumon sous-jacente, et une imagerie thoracique (radiographies) devrait être envisagée.(Traduit par Dr Serge Messier).

A Rare Case of Axillary Extramammary Paget's Disease with an Underlying Adenocarcinoma.

Extramammary Paget's disease (EMPD) is an uncommon cutaneous neoplasm almost exclusively located in the vulvar, perianal, and male genitalia regions. Evaluation and management are complicated given the average delay in diagnosis is two years and approximately 30% of cases are associated with underlying malignancies. The axilla is a unique location for EMPD. We report a rare case of a 78-year-old male with axillary EMPD associated with an underlying adenocarcinoma. A 1-cm tender and pruritic erythematous plaque with surrounding erythema appeared in the patient's axilla. An irritated seborrheic keratosis secondarily impetiginized along with irritant contact dermatitis was suspected. Treatment of cefdinir and topical hydrocortisone failed and a biopsy was taken. Microscopic and immunohistochemical examination showed ulceration with an underlying proliferation of atypical glands (Figure 2A) and a nested intraepidermal proliferation with pagetoid spread (Figure 2B). The atypical cells were positive for gross cystic disease fluid protein 15 (Figure 2C), epithelial membrane antigen (Figure 2D), cytokeratin 5/6, and cytokeratin 7. These findings were supportive of an apocrine adenocarcinoma arising in association with EMPD. Wide location excision was performed. Screening for associated malignancies or lymphatic spread is the primary goal during evaluation. Outcomes are favorable when the primary neoplasm is of limited distribution. The accepted treatment for primary lesions is wide local excision, although anatomic tissue constraints necessitate further research into other treatment modalities. To our knowledge, this is the 14th reported case of axillary EMPD with an underlying adenocarcinoma which may help with identification and management of future cases.

Case series of urachal adenocarcinoma: Imaging features.

ABSTRACT: Urachal adenocarcinoma is an unusual and aggressive form of bladder cancer that arises from urachus, a midline fibrous remnant of allantois. Experience with diagnosing them is limited and differentiating urachal adenocarcinoma from other urachal pathologies like infected urachal cysts may be difficult at times. Differentials of urachal anomalies can be narrowed down by proper assessment of patient demographics, clinical details, lesion morphology, and imaging findings. With this case series of five patients of urachal adenocarcinoma, we have tried describing their clinical manifestation and imaging appearances.

Microsecretory adenocarcinoma of the hard palate: a case report and literature review.

Microsecretory adenocarcinoma (MSA) is a new type of salivary gland neoplasm identified in the 2022 World Health Organization Classification of Head and Neck Tumour (Skalova et al., Head Neck Pathol 16:40-53, 2022) and is characterized by a unique set of histomorphologic and immunohistochemical features and a recurrent MEF2C::SS18 fusion. MSA was initially misdiagnosed as another salivary gland tumour due to its similar morphology; until recently, only fewer than 50 cases were reported. We present a case of MSA of the hard palate with diverse architectural growth patterns, bland cytological features, abundant basophilic intraluminal secretions and fibromyxoid stroma. The tumour cells were positive for the SOX10, S100, and p63 protein and negative for the p40 protein according to immunohistochemistry. SS18 gene rearrangement was demonstrated via break-apart fluorescence in situ hybridization. We also provided a comprehensive literature review and integrated the clinicopathological features, immunophenotype, and molecular alterations of the disease. A comprehensive understanding of MSA enables us to accurately distinguish and categorize MSA from other salivary gland tumours with analogous morphologies.

Plasmonic trimers designed as SERS-active chemical traps for subtyping of lung tumors.

Plasmonic materials can generate strong electromagnetic fields to boost the Raman scattering of surrounding molecules, known as surface-enhanced Raman scattering. However, these electromagnetic fields are heterogeneous, with only molecules located at the 'hotspots', which account for ≈ 1% of the surface area, experiencing efficient enhancement. Herein, we propose patterned plasmonic trimers, consisting of a pair of plasmonic dimers at the bilateral sides and a trap particle positioned in between, to address this challenge. The trimer configuration selectively directs probe molecules to the central traps where 'hotspots' are located through chemical affinity, ensuring a precise spatial overlap between the probes and the location of maximum field enhancement. We investigate the Raman enhancement of the Au@Al2O3-Au-Au@Al2O3 trimers, achieving a detection limit of 10-14 M of 4-methylbenzenethiol, 4-mercaptopyridine, and 4-aminothiophenol. Moreover, single-molecule SERS sensitivity is demonstrated by a bi-analyte method. Benefiting from this sensitivity, our approach is employed for the early detection of lung tumors using fresh tissues. Our findings suggest that this approach is sensitive to adenocarcinoma but not to squamous carcinoma or benign cases, offering insights into the differentiation between lung tumor subtypes.

Colon cancer diagnosis by means of explainable deep learning.

Early detection of the adenocarcinoma cancer in colon tissue by means of explainable deep learning, by classifying histological images and providing visual explainability on model prediction. Considering that in recent years, deep learning techniques have emerged as powerful techniques in medical image analysis, offering unprecedented accuracy and efficiency, in this paper we propose a method to automatically detect the presence of cancerous cells in colon tissue images. Various deep learning architectures are considered, with the aim of considering the best one in terms of quantitative and qualitative results. As a matter of fact, we consider qualitative results by taking into account the so-called prediction explainability, by providing a way to highlight on the tissue images the areas that from the model point of view are related to the presence of colon cancer. The experimental analysis, performed on 10,000 colon issue images, showed the effectiveness of the proposed method by obtaining an accuracy equal to 0.99. The experimental analysis shows that the proposed method can be successfully exploited for colon cancer detection and localisation from tissue images.

[Diagnosis and treatment of small-cell carcinoma of the prostate: A report of 2 cases].

OBJECTIVE: To explore the clinical manifestations, diagnosis, pathological features and treatment of small-cell carcinoma of the prostate (SCCP). METHODS: We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018, and reviewed relevant literature. RESULTS: Both the patients had the symptoms of frequent, urgent and difficult urination, with an elevated level of PSA and gradesⅡ－Ⅲ enlargement of the prostate at palpation. One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor. Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases. One of them was treated by etoposide-platinum (EP) chemotherapy and died of systemic multiple organ failure 20 months after diagnosis, while the other underwent endocrine therapy and has lived with tumor up to the present day. CONCLUSION: The incidence rate of SCCP is low, its malignancy is high, and its prognosis is poor. The average survival of the patient is about 7 to 10 months after diagnosis. Currently there is no effective management of the dissease, except by relying on the experience of the treatment of small-cell lung cancer, with chemotherapy as the main option.

[Diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer in patients with PI-RADS 4-5].

OBJECTIVE: To investigate the diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer (PCa) in patients with prostate imaging reporting and data system v2.1 (PI-RADS v2.1) 4-5. METHODS: From January 2023 to October 2023, patients who underwent prostate biopsy for the first time with total prostate specific antigen (tPSA) ≤ 20 ng/mL and had a multi-parametric magnetic resonance imaging (mpMRI) PI-RADS of 4-5 in Peking University First Hospital were prospectively collected. All the patients underwent transrectal ultrasound-guided cognitive fusion targeted biopsy (3 cores) followed by systematic biopsy (12 cores). Various hypothetical biopsy schemes were defined based on different biopsy sites. The detection effectiveness of targeted biopsy combined with regional systematic biopsy and other biopsy schemes for prostate cancer were compared using Cochran's Q and McNemar tests. RESULTS: A total of 255 patients were enrolled, of whom 204 (80.0%) were detected with prostate adenocarcinoma and 187 (73.3%) were clinically significant with prostate cancer (csPCa). The detection rate of PCa with targeted biopsy was significantly lower than that of targeted biopsy combined with 12-core system biopsy (77.3% vs. 80.0%, P=0.016), and 71.4% (5/7) of the missed patients was csPCa. There was no significant difference in the detection rate between targeted biopsy combined with 4-core regional system biopsy and 12-core system biopsy (P>0.999), and 1 case of csPCa and clinically insignificant prostate cancer (cisPCa) were missed. There was no significant difference in the detection rate of PCa between targeted combined regional system biopsy and targeted combined lateral or traditional 6-core system biopsy and the number of cores were reduced. Missed diagnosis of targeted biopsy was correlated with the maximum diameter of the lesion (OR=0.086, 95%CI: 0.013-0.562, P=0.010). For the patients with PI-RADS 5, only 1 case of PCa was missed in 122 cases by targeted biopsy alone. For patients with PI-RADS 4, 6 PCa cases were missed among the 133 patients with targeted biopsy alone, and 1 case of csPCa and cisPCa were missed by targeted biopsy combined with regional system biopsy. The statistics of positive core counts for different biopsy schemes indicated that targeted combined regional systematic biopsy had a higher proportion of positive cores second only to targeted biopsy alone. CONCLUSION: Targeted biopsy combined with regional systematic biopsy has high diagnostic efficacy in patients with PI-RADS 4-5 and can be considered as one of the improved schemes for combined biopsy. Targeted biopsy alone is also a feasible option for patients for patients with a PI-RADS score of 5.

Esophageal cancer: current status and new insights from inflammatory markers - a brief review.

Esophageal cancer (EC) poses a significant challenge to the healthcare system due to its profound impact on cancer-related morbidity and mortality worldwide. This malignancy ranks among the most arduous conditions confronting the surgeon. EC arises from a complex interplay of genetic predispositions and environmental factors. While the incidence of esophageal adenocarcinoma (EAC) is on the rise in the West, esophageal squamous cell carcinoma (ESCC) remains prevalent in the East. Chronic inflammation plays a pivotal role in the initiation and progression of EC. Accordingly, serum inflammatory markers, growth factors, and cytokines have been shown to be clinically useful. Thus, evaluating serum cytokine levels for EC prediction is a safe and feasible screening method. Given the aggressive nature and poor prognosis of the disease, innovative approaches to diagnosis, prognosis, and management of EC are indispensable. This review discusses the major risk factors and the current landscape of EC, with a specific focus on the potential contributions of new inflammatory markers to enhance disease management and improve patient outcomes.

The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

[Application of PRAME immunohistochemistry in the differential diagnosis of primary endometrial and endocervical adenocarcinomas].

Objective: To investigate the diagnostic value of preferentially expressed antigen in melanoma (PRAME) immunohistochemical staining in differential diagnosis of primary endometrial and endocervical adenocarcinomas. Methods: Eighty-seven cases of endometrial adenocarcinoma and sixty-three cases of cervical adenocarcinoma were collected from May 2018 to November 2023 in the Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and all the cases were subject to PRAME immunohistochemical staining. The difference of PRAME expression between endometrial and endocervical adenocarcinomas was analyzed. Results: In 87 cases of endometrial adenocarcinoma, patients' age ranged from 35 to 71 years (average 59 years, median 59 years); in 63 cases of cervical adenocarcinoma patients' age ranged from 28 to 80 years (average 49 years, median 47 years). Seventy-eight cases (78/87, 89.7%) of endometrial adenocarcinoma; 2 cases (2/63, 3.2%) of cervical adenocarcinoma showed positive PRAME staining, and both cases of cervical adenocarcinoma were clear cell carcinoma. The sensitivity and specificity of PRAME in distinguishing between endometrial and cervical adenocarcinoma in the cohort were 89.7% and 96.8%, while those in differentiating non-clear cell carcinoma of the uterus from that of the cervix reached up to 91% and 100%, respectively. Conclusions: Immunohistochemical staining for PRAME demonstrates statistically significant differences between endometrial and cervical carcinomas, making it a useful auxiliary diagnostic marker for differentiating cervical and endometrial adenocarcinoma, especially non-clear cell carcinoma.

[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

Studies on the association of malondialdehyde as a biomarker for oxidative stress and degree of malignancy in dogs with mammary adenocarcinomas.

BACKGROUND: Mammary adenocarcinomas are one of the most common tumour diseases in bitches. The relationship between oxidative stress and the degree of malignancy of the tumour has not been sufficiently researched in veterinary medicine. OBJECTIVES: The main objective was to investigate the potential role of MDA as a practice-relevant biomarker for the assessment of systemic oxidative stress and to determine whether this parameter can indicate the malignancy grade of a mammary adenocarcinoma. METHODS: In the present pilot study, MDA plasma concentrations were analysed in 55 bitches with (n = 28) and without (n027) malignant adenocarcinomas of the mammary gland using two different measurement methods and the relationship to tumour size was investigated. RESULTS: The mean MDA concentration measured by enzyme-linked immunosorbent assay (ELISA) was 289 ng/mL (range 365-634 ng/mL) in dogs with grade 1 adenocarcinoma (n = 13), 288.5 ng/mL (range 85-752 ng/mL) in dogs with grade 2 adenocarcinoma (n = 10), 332 ng/mL (range 239-947 ng/mL) in dogs with grade 3 (n = 5) adenocarcinoma and 293 ng/mL (range 175-549 ng/mL) in dogs without a mammary tumour (n = 27). When MDA was measured by HPLC, the average MDA concentration in the study group (n = 11) was 0.24 µmol/L (range 0.16-0.37) and that of the control group (n = 15) was 0.27 µmol/L (range 0.16-1.62). Thus, there were no significant differences between the study group with malignant adenocarcinomas and the control group in both examination methods (p > 0.05). Furthermore, there was no correlation between the MDA concentrations and the approximate volume of the mammary tumour. CONCLUSION: The results highlight the challenges of providing a prognosis for the malignancy of a mammary adenocarcinoma based on MDA concentrations in plasma using ELISA or HPLC. As a result, histopathological examination remains the gold standard for diagnosing and differentiating adenocarcinomas of the mammary gland.

Advances in diagnosis and management of cancer of the esophagus.

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.