Immunophenotypic analysis of angiomyolipoma with epithelial cysts, comparison to mixed epithelial and stromal tumors and epithelial and stromal elements of normal kidney and ovaries.

Angiomyolipoma with epithelial cysts (AMLEC) is a rare variant of renal angiomyolipoma (AML). It is characterized by a conventional AML component admixed with epithelial cysts within an "ovarian-like" stroma. Mixed epithelial and stromal tumor (MEST) is another renal neoplasm featuring epithelial cysts and "ovarian-like" stroma. While there is consensus that in MEST the epithelial and stromal components are neoplastic, in AMLEC it has been hypothesized that the epithelial component may represent renal tubular entrapment or ovarian-like transdifferentiation of tumor cells. The aim of this study was to compare the immunophenotypes of the epithelial-stromal components of AMLEC and MEST, with normal kidney and ovary to provide additional insights into the pathogenesis and relationships of these entities. In this study, we analyzed eight cases of AMLEC and 14 cases of MEST from 2003 to 2023. We used tissue microarrays, full sections, or unstained slides with an immunohistochemical panel including renal and ovarian markers: SF1, ER, PR, AR, PAX8, WT1, GATA3, CA-IX, p16, inhibin A, and BCL2. We compared these cases with ten non-neoplastic ovary and kidney samples. Our findings indicate that the epithelial component of AMLEC and MEST resembles hormone receptor positive renal tubular epithelium (AR + /ER - /PR -). AMLEC's stromal component resembled hormone receptor positive renal stroma, while MEST's resembled ovarian stroma, supporting mullerian transdifferentiation. Our study showed that the epithelial and stromal components of AMLEC and MEST are immunophenotypically different and also differ from normal tissues. Our findings suggest that in AMLEC, the epithelial-stromal component represents a hormonally driven proliferation of non-neoplastic renal elements within a dysregulated tumor microenvironment.

Metastatic germ cell tumors in serous cavities and cerebrospinal fluid: A single-center experience.

BACKGROUND: Metastatic germ cell tumors (GCTs) involving body cavity effusions and cerebrospinal fluid (CSF) are rare. Diagnosis is challenging because of limited morphological and clinicopathological information in the literature. METHODS: A database search of our institution from 1990 to 2024 identified 27 cases of metastatic GCTs, comprising five pediatric and 22 adolescent and adult patients, in serous cavities or the CSF, including peritoneal (15), pleural (nine), CSF (two), and pericardial (one) fluid. RESULTS: The most common primary site was the testis (n = 10), followed by the ovaries (n = 7), mediastinum (n = 4), retroperitoneum (n = 3), pineal gland (n = 2), and sacrum/coccyx (n = 1). The primary tumors in 14 patients were mixed GCTs (six with a seminoma component), followed by immature teratomas (six), yolk sac tumors (three), embryonal carcinomas (two), pure seminomas (one), and postpubertal teratomas (one). The median interval between primary tumor diagnosis and diagnosis of fluid positivity was 7 months (range: 0-134 months). In nine cases, the malignant fluid was diagnosed simultaneously with or within 1 month of the primary tumor. GCT subtyping was performed on 23 of the 27 cytological specimens. Twenty-four patients (89%) also had metastases to other sites. Thirteen patients died of the disease (48%), with a median survival time of 4 months. CONCLUSIONS: Metastatic GCTs in serous effusions and CSF are often associated with disseminated disease and poor prognosis. Subtyping can be performed by cytomorphology combined with immunohistochemistry.

Incidental findings during donor liver assessment: Single center experience.

Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18-70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.

Painful Granulomatous Hashimoto Thyroiditis Uncovered Systemic Histoplasmosis.

Background. Granulomatous thyroiditis is usually viral and very rarely due to fungal infection. Fungal thyroiditis affects the severely immunocompromised and only rarely immunocompetent individuals. Case report. A 32-year-old man with known Hashimoto thyroiditis was consulted for a 1-week history of neck pain, dysphagia, cough, asthenia, loss of appetite, and night sweats. Imaging showed an enlarged right thyroid lobe. Laboratory studies confirmed hypothyroidism. He underwent a thyroid lobectomy. Microscopic examination showed granulomas in a background of Hashimoto thyroiditis. Silver stain revealed numerous yeasts consistent with Histoplasma. Subsequent serology was also positive. Further evaluations were negative for acquired or constitutional immunodeficiencies. He was started on oral itraconazole with resolution of all constitutional symptoms. Conclusions. We report a second case of concurrent Hashimoto and Histoplasma thyroiditis in an immunocompetent patient. Systemic manifestations of fungal infection are confounded by systemic symptoms of thyroid dysfunction. Fungal thyroiditis is a manifestation of systemic fungal infection requiring prolonged systemic therapy to prevent complications or fatal outcomes.

Metabolic Interplay in the Tumor Microenvironment: Implications for Immune Function and Anticancer Response.

Malignant tumors exhibit rapid growth and high metabolic rates, similar to embryonic stem cells, and depend on aerobic glycolysis, known as the "Warburg effect". This understanding has enabled the use of radiolabeled glucose analogs in tumor staging and therapeutic response assessment via PET scans. Traditional treatments like chemotherapy and radiotherapy target rapidly dividing cells, causing significant toxicity. Despite immunotherapy's impact on solid tumor treatment, gaps remain, leading to research on cancer cell evasion of immune response and immune tolerance induction via interactions with the tumor microenvironment (TME). The TME, consisting of immune cells, fibroblasts, vessels, and the extracellular matrix, regulates tumor progression and therapy responses. TME-targeted therapies aim to transform this environment from supporting tumor growth to impeding it and fostering an effective immune response. This review examines the metabolic disparities between immune cells and cancer cells, their impact on immune function and therapeutic targeting, the TME components, and the complex interplay between cancer cells and nontumoral cells. The success of TME-targeted therapies highlights their potential to achieve better cancer control or even a cure.

Acinic Cell Carcinoma in the 21st Century: A Population-Based Study from the SEER Database and Review of Recent Molecular Genetic Advances.

BACKGROUND: Acinic cell carcinoma (AciCC) comprises 6-7% of all salivary gland neoplasms and is the second most common salivary gland malignancy in children. Like many salivary gland carcinomas, it is considered low grade but occasionally it behaves aggressively. Understanding the risk factors associated with recurrence, metastasis, and death is important to determine the counseling and management of individual patients. Older population-based studies are presumed to have been confounded by the misclassification of other neoplasms as AciCC, in particular secretory carcinoma and cystadenocarcinoma. Since diagnostic tools to reliably separate these entities have been available for over a decade, reevaluation of epidemiologic data limited to the 21st century should allow a better characterization of the clinicopathological characteristics of AciCC. METHODS: Our study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2000 to 2018. Cox regression model analysis was performed to identify risk factors independently affecting survival. RESULTS: Data for 2226 patients with AciCC were extracted from the database. Most patients were females: 59%, and white: 80.5%, with a mean age at diagnosis of 51.2 (SD ± 18.7) years. Most cases (81%) were localized at presentation. Tumor size was less than 2 cm in 42%, 2-4 cm in 47%, and >4 cm in 11%. Low-grade tumors had 5-year survival > 90%, whereas high-grade tumors had survival < 50%. Of the patients with known lymph node status only 7.3% had nodal metastases. Distant metastases were documented in 1.1%, involving lungs 44%, bone 40%, liver 12%, and brain 4%. The most common treatment modality was surgery alone: 63.6% followed by surgery and adjuvant radiation: 33%. A few received chemotherapy (1.8%) or multimodality therapy (1.2%). The 5-year overall survival rate was 90.6% (95%CI 89.1-91.9), and disease-specific survival was 94.6% (95%CI 93.3-95.6). Multivariable cox regression analysis showed that undifferentiated (HR = 8.3) and poorly differentiated tumor grade (HR = 6.4), and metastasis (HR = 5.3) were the worst independent prognostic factors. Other poor risk factors included age > 50 (HR = 3.5) and tumor size > 4 cm (HR = 2.5). CONCLUSIONS: In the US, AciCC is more common in middle age white females, and most tumors are less than 4 cm and localized at diagnosis. The most relevant negative prognostic factor was high tumor grade which was associated with higher hazard ratios for death than all other variables, including regional or distant metastases at presentation.

Amyloid Deposition in the Upper Aerodigestive Tract, A Single Institute Experience.

Objectives: The purpose of this study is to evaluate clinical information, laboratory results, and pathologic findings of patients with amyloidosis involving larynx, oral cavity, and pharynx from our institute. Methods: A total of 39 specimens from 28 patients were retrieved from 2000 to 2020. Data collection included clinical presentation, radiographic, laboratory results, and pathologic findings. Results: A total of 12 patients had laryngeal amyloidosis and true vocal cord was the most common location. Protein electrophoresis detected monoclonal protein in 10% (1/10) of patients tested. Two patients had hematopoietic disorder (2/12, 17%) and another patient had a peptide profile consistent with amyloid transthyretin (ATTR) detected by mass spectrometry. Twelve patients showed amyloidosis in the oral cavity with 75% involving the tongue. Monoclonal protein was found in 89% of cases tested. Nine patients (9/12, 75%) had systematic involvement including 6 with hematopoietic malignancy and 3 with biopsy-confirmed systemic light chain amyloidosis. Compared to the laryngeal amyloidosis, amyloid deposition in oral cavity had a significant higher association with systematic disease (P < .01). Pharyngeal amyloidosis was seen in 7 patients. Three of 6 patients tested (3/6, 50%) were found to have biopsy-confirmed hematopoietic malignancy. Conclusions: Laryngeal amyloidosis is mostly a localized disease. Amyloidosis involving oral cavity is associated with significantly higher risk of systematic involvement which warrants a comprehensive laboratory, radiographic, and pathologic workup. There is limited data about pharynx amyloidosis. Oropharynx and hypopharynx amyloidosis appear to be more likely associated with underlying hematologic malignancy compared to nasopharynx involvement.

Metastatic solid tumors to the testis: a clinicopathologic evaluation of 157 cases from an international collaboration.

To elucidate the spectrum of metastatic solid tumors to the testis and their clinicopathologic features. The databases and files of 26 pathology departments from 9 countries on 3 continents were surveyed to identify metastatic solid tumors to the testis and to characterize their clinicopathologic features in detail. We compiled a series of 157 cases of metastatic solid tumors that secondarily involved the testis. The mean patient age at diagnosis was 64 years (range, 12-93 years). Most patients (127/144; 88%) had clinical manifestation of the disease, with testicular mass/nodule (89/127; 70%) being the most common finding. The main mechanism of testicular involvement was metastasis in 154/157 (98%) cases. Bilateral testicular involvement was present in 12/157 (8%) patients. Concurrent or prior extratesticular metastases were present in 78/101 (77%) patients. The diagnosis was made mainly in orchiectomy specimens (150/157; 95%). Different types of carcinomas (138/157; 87%), most commonly adenocarcinoma (72/157; 46%), were the most common malignancies. The most common primary carcinomas included prostatic (51/149; 34%), renal (29/149; 20%), and colorectal (13/149; 9%). Intratubular growth was identified in 13/124 (11%) cases and paratesticular involvement was found in 73/152 (48%) cases. In patients with available follow-up (110/157; 70%), more than half (58/110; 53%) died of disease. In this largest series compiled to date, we found that most secondary tumors of the testis represent metastases from the genitourinary and gastrointestinal tract carcinomas and typically occur in the setting of disseminated disease.

Comparison of PD-L1 IHC 22C3 PharmDx Combined Positive Score (CPS) in Primary Versus Metastatic Nodal Squamous Cell Carcinomas of the Head and Neck: Is There a Significant Difference?

PD-L1 IHC 22C3 pharmDx is an FDA-approved companion test to select patients for anti-PD-L1 immunotherapy. In head and neck squamous cell carcinoma PD-L1 expression is determined using a Combined Positive Score (CPS), which evaluates expression in tumor cells and tumor-associated leukocytes. We hypothesized that in nodal metastasis, the CPS should be higher given their inherent higher proportion of leukocytes. A significant difference in CPS between sites would mean that the tissue chosen for PD-L1 testing would impact patient eligibility for therapy. Currently, guidelines about which tissue should be tested do not exist. PD-L1 22C3 IHC was performed in the primary and nodal metastases of 35 head and neck squamous cell carcinoma, and a CPS was generated by 3 pathologists. Mean CPS was higher at the primary than the nodal metastasis: 47.2 versus 42.2; however, the difference was not statistically significant: P=0.259 . By therapeutic groups: negative (CPS <1), low (CPS 1-19) and high (CPS≥20), low-expression was more common in the primary: 40 vs. 26%, and high-expression in the nodal metastasis: 74 vs. 60% but this difference was not statistically significant: P=0.180. Stratified by positive versus negative (CPS <1 vs. ≥1), there were no differences between sites. Interobserver agreement for CPS among the 3 raters was slight for both sites: ƙ = 0.117 and 0.025, fair if stratified by therapeutic group: ƙ = 0.371 and 0.318, and near perfect if stratified as negative versus positive: ƙ = 0.652 and 1. There were no statistically significant differences in CPS between primary and nodal metastases independent of how the CPS was stratified.

Jejunal Intussusception Secondary to a Large Inflammatory Fibroid Polyp: A Case Report and Discussion of Differential Diagnosis.

Inflammatory fibroid polyp (IFP), initially considered a reactive process, is now recognized as a benign mesenchymal neoplasm of the gastrointestinal tract. We report a case of a 68-year-old woman with medically refractory Crohn disease that presented with intussusception requiring surgical intervention. The resection revealed a jejunal mass consisting of a submucosal proliferation of bland spindle cells in a fibrous stroma infiltrated by numerous eosinophils. By immunohistochemistry, the lesion was positive for vimentin and negative for desmin, smooth muscle actin (SMA), S-100, CD117, DOG1, ALK (D5F3), Melan-A, HMB-45, CD34, and STAT6. Ki-67 proliferative index was low (<1%). The mass was classified as IFP by its characteristic morphology and associated eosinophilia. IFP should be considered in the differential diagnosis of adults with intussusception or bowel obstruction. Definitive treatment typically requires surgical resection of the involved bowel segment.

Comparison of endoscopic ultrasound-guided fine needle aspiration cytology versus endoscopic biopsy for the diagnosis of subepithelial lesions of the upper and lower gastrointestinal tract: A 10-year retrospective single institution analysis.

BACKGROUND: The aim of this study is to compare the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) versus endoscopic biopsy for the diagnosis of gastrointestinal (GI) subepithelial lesions (SELs) using surgical resection as the gold standard. METHODS: All patients who underwent EUS-FNA of upper and lower GI SELs over a 10-year period (2010 through 2019) were retrospectively reviewed. The medical records of all patients were reviewed and data extracted from the endoscopy, pathology, and surgical reports were analyzed. RESULTS: In total, 283 patients with ages ranging from 21 to 92 years underwent EUS-FNA for evaluation of GI SELs, 117 (41%) patients underwent endoscopic biopsy and 82 (29%) patients had concurrent surgical resection specimen. EUS-FNA was obtained from the stomach in 167 (59%) patients, duodenum in 51 (18%) patients, esophagus in 38 (13%) patients, and colorectum in 27 (10%) patients. It was found that the largest percentage of lesions originated in the muscularis propria (36%), followed by the submucosa (26%), deep mucosa (13%), and not specified in 21%. The concordance between EUS-FNA and endoscopic biopsy was good (correlation coefficient of 0.631, p < .001). EUS-FNA versus endoscopic biopsy in resected cases showed sensitivity and specificity of 78% versus 68% and 84% versus 100%, respectively. The EUS-FNA has an accuracy of 80% compared to 74% in biopsy. The diagnostic yield of EUS-FNA and endoscopic biopsy was 64% versus 55%. CONCLUSION: EUS-FNA is more sensitive and more accurate than endoscopic biopsy for diagnosing GI SELs with a good concordance between the two techniques.

Pulmonary large cell neuroendocrine carcinoma (LCNEC): a population-based study addressing recent molecular-genetic advances and emerging therapeutic approaches.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare, aggressive cancer most commonly found in the lungs but not exclusively, with a worse prognosis than non-small cell lung carcinomas. Currently, LCNEC patients are treated using small cell and non-small cell protocols. This study aims to use the SEER database to identify demographic, clinical, pathological, and therapeutic factors affecting the prognosis and survival of patients with LCNEC of the lung. METHODS: Demographic, clinical, and management data of patients with lung LCNEC were extracted from the SEER database for the period 2000-2018. RESULTS: In the USA, LCNEC has a higher incidence in elderly white men: M:F ratio = 1.2:1, Caucasian: 83.3%, mean age: 67 ± 10.2 years. The most common treatment modality was chemotherapy only: 29.2%, followed by surgery: 21.5% (but in this group the statuses of chemotherapy were unknown), and combination surgery/chemotherapy: 8.8%. The overall and cause-specific 5-year survival was 17.5% (95% CI 16.3-18.8) and 21.9% (95% CI 20.5-23.4), respectively. By treatment, the best 5-year survival was for surgery alone (48%), followed by multimodality therapy (chemo + surgery + radiation) at 35% (95% CI 27-43). Age > 60 years, male gender, size > 7 cm, and nodal and liver metastasis were independent risk factors associated with increased mortality. CONCLUSION: Lung LCNEC is an aggressive neoplasm most common in older white males that presents at an advanced stage despite small primary tumors. Most patients die within 2 years. The best predictor of survival is surgery with chemotherapy. Given its dismal prognosis, new treatment guidelines are needed for this aggressive cancer.

EBV-Gastritis Preceded the Development of Nasopharyngeal EBV (+) Diffuse Large B Cell Lymphoma in a Patient With Ruxolitinib-Induced Immunosuppression.

Epstein-Barr virus (EBV) is acquired early in life as asymptomatic or symptomatic infectious mononucleosis (IM) and remains latent in a few B cells in most individuals. Pathologic EBV-reactivation affects immunosuppressed individuals and manifests as IM-like syndromes, polyclonal lymphoproliferative disorders, EBV-related lymphomas, and carcinomas. EBV-associated gastritis is an underrecognized and very rarely reported entity. We report a case of a 65-year-old woman with ruxolitinib-treated polycythemia vera, who developed EBV viremia and EBV gastritis. The patient improved after the ruxolitinib dose reduction and administration of antiviral therapy. A few months after discontinuation of the antiviral therapy the gastric symptoms recurred, numerous gastric ulcers were identified, and a nasopharyngeal mass was detected. A biopsy of the nasopharynx showed an EBV (+) diffuse large B cell lymphoma. Ruxolitinib was discontinued and the patient was started on rituximab monotherapy with a resolution of symptoms and pathologic improvement. Our case supports earlier reports of an association of ruxolitinib therapy with EBV complications. An early diagnosis of EBV gastritis in immunocompromised patients is important since the gastric infection may precede or co-exist with a developing EBV-associated malignancy. Our case and existing literature suggest that EBV gastritis in symptomatic patients with iatrogenic immunosuppression requires discontinuation of immunosuppressive therapy if feasible, treatment with antivirals, and close surveillance for possible evolving/concurrent EBV (+) malignancy.

Differential Diagnosis of Cystic Lesions of the Spleen: A Review of Clinical, Imaging and Pathological Findings.

Cystic lesions of the spleen are being noticed with increased frequency as "incidentalomas" during imaging work-up for unrelated causes. As a group, these lesions encompass pure cystic and mixed cystic and solid, benign and malignant processes that in general require a tissue sample for definitive diagnosis. In this review, we will describe the differential diagnosis of cystic lesions of the spleen, highlighting key imaging, clinical and pathologic findings.

Cobas HPV Genotyping of FNA Sample Supernatant and Frozen Section Scrapings of Suspected Head and Neck Cancer.

The human papillomavirus (HPV) status of squamous cell carcinomas (SCCs) of the head and neck is relevant for therapy planning, staging, and follow-up. Immunohistochemistry (IHC) for p16 is a surrogate marker of HPV status in oropharyngeal SCC, but not at other head and neck sites. We tested if the cobas HPV test was feasible and superior to p16-IHC on fine-needle aspiration (FNA) supernatants and frozen section (FS) scrapings of suspected SCC. A 500 µL aliquots of postcentrifugation supernatant CytoRich Red media of FNA cellblock specimens and scrapings of FS suspended in SurePath media vials were tested with the cobas HPV test and compared with p16-IHC and/or HPV in situ hybridization (ISH) performed on cellblock and/or resections. Twenty-nine (n=29) FNAs were tested for a cobas HPV test, p16, and/or HPV-ISH. The mean collection to testing time was 6.3 days (range: 0 to 24 d). Cobas yielded valid results in all cases; p16-IHC could not be interpreted in 4 (13%) cellblocks; correlation was performed on subsequent resections. Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FNA samples was 0.9, perfect agreement, sensitivity 100%, specificity 92.3%, positive predictive value 94.1%, negative predictive value 100%. Thirty-four (n=34) scrapings from FS were tested for cobas, p16, and/or HPV-ISH. The mean collection to testing time was 10.4 days (range: 1 to 28 d). Cohen κ correlation for cobas versus p16-IHC/HPV-ISH on FS scrapings was 1, perfect agreement. Sensitivity, specificity, positive predictive value, and negative predictive value was 100%. Cobas genotype was HPV-16 in 87%, HPV-18 in 3%, and HPV-other in 10%. Cobas HPV test in FNA supernatant and FS scrapings outperformed or was equivalent to p16-IHC and provided genotyping information.

A Consensus Diagnosis Utilizing Surface KI-67 Expression as an Ancillary Marker in Low-Grade Dysplasia Helps Identify Patients at High Risk of Progression to High-Grade Dysplasia and Esophaegal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) develops in a step-wise manner, from low-grade dysplasia (LGD) to high-grade dysplasia (HGD), and ultimately to invasive EAC. However, there remains diagnostic uncertainty about LGD and its risk of progression to HGD/EAC. The aim is to investigate the role of Ki-67, immune-histochemical marker of proliferation, surface expression in patients with confirmed LGD, and risk stratify progression to HGD/EAC. A retrospective cohort study was conducted. Patients with confirmed LGD and indefinite for dysplasia (IND), with a mean follow-up of ≥1 year, were included. Pathology specimens were stained for Ki-67 and analyzed for evidence of surface expression. Our results reveal that 29% of patients with confirmed LGD who stained positive with Ki-67 progressed to HGD/EAC as opposed to none (0%) of the patients who stained negative, a statistically significant result (P = 0.003). Similarly, specimens from patients with IND were stained and analyzed revealing a nonsignificant trend toward a higher rate of progression for Ki-67 positive cases versus Ki-67 negative, 30% versus 21%, respectively. Ki-67 expression by itself can identify patients with LGD at a high risk of progression.

Quantification of the presence of enzymes in gelatin zymography using the Gini index.

Gel zymography quantifies the activity of certain enzymes in tumor processes. These enzymes are widely used in medical diagnosis. In order to analyze them, experts classify the zymography spots into various classes according to their tonalities. This classification is done by visual analysis, which is what makes it a subjective process. This work proposes a methodology to carry out this classifications with a process that involves an unsupervised learning algorithm in the images, denoted as the GI algorithm. With the experiments shown in this paper, this methodology could constitute a tool that bioinformatics scientists can trust to perform the desired classification since it is a quantitative indicator to order the enzymatic activity of the spots in a zymography.

Incidental adrenal hemangioma clinically suspicious for malignancy: diagnostic considerations and review of the literature.

Adrenal hemangiomas are rare lesions often found incidentally during unrelated diagnostic work-up. We report a case of a 67-year-old man with history of hypertension, hyperlipidemia, anemia, arthralgia, joint swelling and unexplained weight loss, which prompted imaging studies. Computed tomography scan revealed a 5.4 cm adrenal mass. The patient had no clinical manifestations of adrenal medullary or cortical hyperfunction. Urine and plasma metanephrines and aldosterone/renin ratio were within normal range. The patient was taking prednisone for hand and ankle swelling, precluding assessment for Cushing syndrome. Given the size of the lesion, the possibility of malignancy was considered, and the patient elected for surgical management. The left adrenalectomy specimen weighed 54 g and revealed a 4.9 cm tan-brown mass with congested cut surface and a thin rim of residual adrenal gland parenchyma. Histologic examination showed thick and thin-walled vessels intermingled with adrenocortical elements at the periphery characteristic of a hemangioma. Surgical resection is the mainstay treatment for large, isolated adrenal masses to exclude malignancy and prevent retroperitoneal hemorrhage. Herein, we report a case of adrenal hemangioma, review a variety of other diagnostic considerations occurring in the adrenal gland, and highlight useful distinguishing features to assist in accurate diagnosis.

Gastrointestinal Stromal Tumors (GIST): A Population-Based Study Using the SEER Database, including Management and Recent Advances in Targeted Therapy.

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) system. Most GISTs originate from the interstitial cells of Cajal (ICC), the pacemaker cell situated between the circular and longitudinal layers of the muscularis propria along the GI tract. In this population-based study using the SEER database, we sought to identify demographic, clinical, and pathologic factors that affect the prognosis and survival of patients with this neoplasm. Molecular genetic advances, current management guidelines, and advances in targeted therapy are discussed. Methods: Demographic and clinical data from GIST patients were retrieved from the SEER research plus database for the period 2000−2018. Statistical analysis was performed with IBM SPSS® v20.2 software using the Chi-square test, paired t-test, multivariate analysis, and Kaplan−Meier functions. Results: A total of 10,833 patients with GIST were identified. Most patients were between 60−74 years of age: 40%, Caucasian: 68%, and the male to female ratio was 1.1:1. The most common primary tumor sites were stomach: 63%, small intestine: 30%, rectum: 3%, and esophagus: 0.7%. When reported, the grade of differentiation was well: 38%, moderately: 32%, undifferentiated: 19%, poorly: 12%. The size of most tumors ranged between 6−10 cm: 36% and they were treated by surgical intervention: 82% and/or chemotherapy/targeted therapy: 39%. The stage was localized: 66%, advanced: 19%, and regional: 15%. The 5-year survival was 74% (95% confidence interval (95% CI) = 72.6−74.7), and the 5-year cause-specific survival 82% (95% CI = 80.7−82.6). The 5-year cause-specific survival by treatment included surgery at 86% (95% CI = 85.4−87.3), chemotherapy/targeted therapy with or without surgery at 77% (95% CI = 75.7−78.9), and radiation at 75% (95% CI = 74.5−80). On multivariable analysis tumor size > 5 cm, poorly and undifferentiated grade, age > 60, and distant metastases at presentation were associated with worse overall survival. Conclusion: GISTs comprise 1−2% of malignancies of the GI tract, usually affect male Caucasians between the ages of 60 and 74 years, most tumors occur in the stomach and small intestine, and are usually >5 cm, but still localized, at the time of diagnosis. Most tumors receive multimodality surgical and chemotherapy/targeted therapy treatment, with a 5-year overall survival of 74% and cause-specific survival of 82%. GIST patients would benefit from enrollment in large clinical trials to establish better therapy guidelines for unresectable, treatment-refractory, and recurrent tumors.