Acanthosis nigricans - a potentially useful clue to the presence of significant occult disease at autopsy.

A 19-year-old male was found dead in his apartment. At autopsy he was morbidly obese (Body mass index; BMI - 40.5) with multiple areas of velvety pigmented thickening of the skin in folds around the neck, in the axillae, in the inframammary regions, over the anterior waistline and groin regions and over the dorsal aspects of the feet. These had the typical appearance of acanthosis nigricans. Internal examination revealed aspiration of gastric contents into the airways. Vitreous humour biochemistry showed markedly elevated levels of both glucose (62.9 mmol/L) and ß-hydroxybutyrate (13.54 mmol/L). Death was, therefore, due to aspiration pneumonia complicating diabetic ketoacidosis on a background of morbid obesity. The initial indicator of underlying diabetes, in conjunction with obesity had been acanthosis nigricans.

Clinical benefit of baseline imaging in Merkel cell carcinoma: Analysis of 584 patients.

BACKGROUND: Merkel cell carcinoma (MCC) guidelines derive from melanoma and do not recommend baseline cross-sectional imaging for most patients. However, MCC is more likely to have metastasized at diagnosis than melanoma. OBJECTIVE: To determine how often baseline imaging identifies clinically occult MCC in patients with newly diagnosed disease with and without palpable nodal involvement. METHODS: Analysis of 584 patients with MCC with a cutaneous primary tumor, baseline imaging, no evident distant metastases, and sufficient staging data. RESULTS: Among 492 patients with clinically uninvolved regional nodes, 13.2% had disease upstaged by imaging (8.9% in regional nodes, 4.3% in distant sites). Among 92 patients with clinically involved regional nodes, 10.8% had disease upstaged to distant metastatic disease. Large (>4 cm) and small (<1 cm) primary tumors were both frequently upstaged (29.4% and 7.8%, respectively). Patients who underwent positron emission tomography-computed tomography more often had disease upstaged (16.8% of 352), than those with computed tomography alone (6.9% of 231; P = .0006). LIMITATIONS: This was a retrospective study. CONCLUSIONS: In patients with clinically node-negative disease, baseline imaging showed occult metastatic MCC at a higher rate than reported for melanoma (13.2% vs <1%). Although imaging is already recommended for patients with clinically node-positive MCC, these data suggest that baseline imaging is also indicated for patients with clinically node-negative MCC because upstaging is frequent and markedly alters management and prognosis.

NR2F1 stratifies dormant disseminated tumor cells in breast cancer patients.

BACKGROUND: The presence of disseminated tumor cells (DTCs) in bone marrow (BM) is an independent prognostic factor in early breast cancer but does not uniformly predict outcome. Tumor cells can persist in a quiescent state over time, but clinical studies of markers predicting the awakening potential of DTCs are lacking. Recently, experiments have shown that NR2F1 (COUP-TF1) plays a key role in dormancy signaling. METHODS: We analyzed the NR2F1 expression in DTCs by double immunofluorescence (DIF) staining of extra cytospins prepared from 114 BM samples from 86 selected DTC-positive breast cancer patients. Samples collected at two or more time points were available for 24 patients. Fifteen samples were also analyzed for the proliferation marker Ki67. RESULTS: Of the patients with detectable DTCs by DIF, 27% had ≥ 50% NR2F1high DTCs, chosen a priori as the cut-off for "dormant profile" classification. All patients with systemic relapse within 12 months after BM aspiration carried ≤ 1% NR2F1high DTCs, including patients who transitioned from having NR2F1high-expressing DTCs in previous BM samples. Of the patients with serial samples, half of those with no relapse at follow-up had ≥ 50% NR2F1high DTCs in the last BM aspiration analyzed. Among the 18 relapse-free patients at the time of the last DTC-positive BM aspiration with no subsequent BM analysis performed, distant disease-free intervals were favorable for patients carrying ≥ 50% NR2F1high DTCs compared with those with predominantly NR2F1low DTCs (p = 0.007, log-rank). No survival difference was observed by classification according to Ki67-expressing DTCs (p = 0.520). CONCLUSIONS: Our study translates findings from basic biological analysis of DTC dormancy to the clinical situation and supports further clinical studies of NR2F1 as a marker of dormancy.

Adenocarcinoma of the Lung Masquerading As Invasive Pulmonary Aspergillosis in an Elderly Lady: A Diagnostic Challenge.

A 59-year-old hypertensive woman presented with a year-long history of cough, expectoration, and progressive breathlessness, recently complicated by hemoptysis and significant weight loss. Initial investigations, including a chest x-ray and contrast-enhanced computed tomography (CECT) of the thorax, suggested an infective pathology. Despite negative bacterial, fungal, and tuberculosis cultures, elevated bronchoalveolar lavage (BAL) galactomannan and serum Aspergillus-specific IgG levels led to a diagnosis of invasive pulmonary aspergillosis (IPA), and antifungal treatment commenced. The patient's initial response was positive; however, symptoms recurred three months later. Further investigations revealed adenocarcinoma, confirmed by cytology from a thoracentesis. The patient, a non-smoker, began targeted therapy with tyrosine kinase inhibitors but declined further diagnostic evaluation. Despite the poor prognosis and palliative care options, the patient opted for discharge to home care. This case underscores the complexity of diagnosing lung pathologies and the importance of considering alternative diagnoses in persistent respiratory symptoms.

Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma.

OBJECTIVES: This study aims to investigate the utility of adjuvant radiation in patients who undergo surgical resection for the management of node-negative sinonasal adenocarcinoma (SNAC). STUDY DESIGN: Retrospective database review. METHODS: The 2004-2016 National Cancer Data Base (NCDB) was used to extract patients with surgically resected node-negative SNAC. Kaplan-Meier survival analysis and Cox-Proportional Hazards Modelling were used to analyze the impact of adjuvant radiation on overall survival (OS) following surgery. RESULTS: 349 patients with SNAC underwent surgical resection. Of these patients, 154 (44.1%) received adjuvant radiotherapy (RT). Although there was no significant difference in race, age, or sex of those receiving RT, those receiving RT have more advanced diseases and are more likely to have positive margins. Kaplan Meier analysis showed no significant difference in 5-year OS in patient who received adjuvant RT in comparison to those who underwent surgical resection alone (65.7% vs. 72.6%, respectively; p = 0.378). In addition, when looking at only patients with positive margins, 5-year OS still did not have a significant difference (73.8% vs. 61.6%, respectively; p = 0.101). Only patients with clinical AJCC T4 showed a statistically significant survival benefit with adjuvant RT (56.9% vs. 29.9%, respectively; p = 0.009). CONCLUSIONS: Adjuvant RT does not appear to provide a significant survival benefit in patients with resected SNAC, with the exception of those with clinically AJCC T4 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2603-2612, 2023.

Utility of Elective Neck Dissection in Clinically Node-Negative Parotid Malignancy.

OBJECTIVE: We sought to investigate the utility of elective neck dissection (END) in clinically node-negative parotid malignancy through the evaluation of factors that are associated with receiving END and survival analysis of patients who received END. STUDY DESIGN: Retrospective cohort database study. SETTING: The National Cancer Database (NCDB). METHODS: The NCDB was used to extract patients with clinically node-negative parotid malignancy. END was defined as having 5 or more lymph nodes examined pathologically, as previously defined in the literature. Univariate and multivariate analyses were used to compare predictors of receiving END, rates of occult metastasis, and survival. RESULTS: Of the 9405 included patients, 3396 (36.1%) underwent an END. END was most frequently performed for squamous cell carcinoma (SCC) and salivary duct histology. All other histologies were significantly less likely to undergo END compared to SCC (p < .05). Salivary ductal carcinoma and adenocarcinoma had the greatest rates of occult node disease (39.8% and 30.0%, respectively), followed by SCC (29.8%). Kaplan-Meier survival analysis showed a statistically significant increase in 5-year overall survival in patients who received END with poorly differentiated mucoepidermoid (56.2% vs 48.5%, p = .004) along with moderately and poorly differentiated SCC (43.2% vs 34.9%, p = .002; 48.9% vs 36.2%, p < .001, respectively). CONCLUSION: Histological classification is a benchmark for determining which patients should receive an END. We demonstrated an increase in overall survival in patients who undergo END with poorly differentiated tumors of mucoepidermoid and SCC histology. As such, histology should be considered along with clinical T-stage and rate of occult nodal metastasis to determine eligibility for END.

Acute Appendicitis During Coronavirus Disease 2019 (COVID-19): Increasing Incidence of Complicate Appendicitis, Severity and Length of Hospitalization.

BACKGROUND/AIM: COVID-19 is rapidly spreading, and due to the high morbidity and mortality caused by the pandemic many Governments have introduced social restrictions. Those measures combined with infection-related patient anxiety, led to hiding other diseases. The aim of this study was to evaluate the impact of COVID-19 on numbers and severity of acute appendicitis cases referred during the pandemic. PATIENTS AND METHODS: Between March 2019 and March 2021, all patients who underwent appendectomy in Tor Vergata Hospital, Rome were included. Patients were divided in two groups (COVID-19/pre-COVID-19). Clinical features, intraoperative findings, hospital stay, and histologic examination data were included in the retrospective analysis. RESULTS: Out of 334 admitted patients, 36 (10.7%) had a diagnosis of acute appendicitis (COVID-19 group) vs. 59(11.2%) in the pre-COVID-19 group. The COVID-19 group presented significantly longer hospitalization, incidence of appendicular abscess, perforation, and severity of inflammation at univariate analysis p=0.002, p=0.021, p=0.001, p=0.006, p=0.001, respectively. At multivariate analysis, appendicular abscess (p=0.015) and higher serum levels of C reactive protein (p<0.008) were associated with prolonged hospital stay. CONCLUSION: This study highlights the correlation between COVID-19 pandemic and the severity of acute appendicitis presentations.

Bilateral papillary thyroid cancer in children: Risk factors and frequency of postoperative diagnosis.

BACKGROUND: The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children. METHODS: A retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed. Bilateral disease was defined as pathologic PTC in the contralateral lobe, including microscopic disease. RESULTS: Of the 172 patients included, 38.4% had bilateral disease with 23% diagnosed postoperatively. Multifocal disease on ultrasound was associated with bilateral disease (OR 2.9, 95% CI 1.5-5.9, p = 0.002). Nodule dimension >2 cm was associated with increased risk for postoperative bilateral disease (OR 3.5, 95% CI 1.6-7.4, p = 0.001). Patients with bilateral disease were more likely to have extrathyroidal extension, lymphovascular invasion, positive central lymph nodes, and extranodal extension (p < 0.001 for all). Diffuse-sclerosing variant PTC was also associated with bilateral disease. CONCLUSION: Thirty-eight percent of children were diagnosed with PTC demonstrate bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. Thus, TT is the appropriate surgical approach for pediatric patients with PTC. TYPE OF STUDY: Clinical Research, Retrospective Review. LEVEL OF EVIDENCE: Level IV.

Detection and Clinical Significance of Circulating Tumor Cells in Patients Undergoing Radical Cystectomy for Urothelial Bladder Cancer.

INTRODUCTION: Estimation of prognosis is patients undergoing radical cystectomy is often unreliable, as occult disease remains undetected by conventional diagnostic tools. The purpose of this study was to evaluate the feasibility and the clinical significance of a polymerase chain reaction assay to detect cytokeratin 7 (CK7) mRNA expression in peripheral blood cells of patients undergoing radical cystectomy for clinically nonmetastatic bladder cancer. PATIENTS AND METHODS: From 2005 to 2009, 59 patients undergoing radical cystectomy and pelvic lymph node dissection were prospectively investigated. Peripheral blood was collected prior to surgery, and a nested polymerase chain reaction assay was developed to identify patients with circulating cells expressing CK7 mRNA. Preoperative, histopathologic data and clinical outcome were compared with CK7 findings. RESULTS: CK7 expression was detected in 23 (38.9%) of 59 patients and correlated to T stage and lymph node status. After a median follow-up of 42 months, 29 patients experienced a recurrence, whereas 36 died. The presence of CK7-positive cells was significantly associated with an increased risk for recurrence and decreased survival as compared with patients who were CK7-negative (P < .001 and P < .001, respectively; hazard ratios of 8.77 and 5.2 for recurrence and overall death, respectively). The detection of CK7-positive cells was an independent predictor of recurrence and death in a multivariable analysis. CONCLUSION: The detection of CK7 mRNA in the circulating cells of patients undergoing radical cystectomy for urothelial cancer identifies those with significantly increased risk of cancer recurrence and death.

Whole-volume vs. segmental CT texture analysis of the liver to assess metachronous colorectal liver metastases.

PURPOSE: It is unclear whether changes in liver texture in patients with colorectal cancer are caused by diffuse (e.g., perfusional) changes throughout the liver or rather based on focal changes (e.g., presence of occult metastases). The aim of this study is to compare a whole-liver approach to a segmental (Couinaud) approach for measuring the CT texture at the time of primary staging in patients who later develop metachronous metastases and evaluate whether assessing CT texture on a segmental level is of added benefit. METHODS: 46 Patients were included: 27 patients without metastases (follow-up >2 years) and 19 patients who developed metachronous metastases within 24 months after diagnosis. Volumes of interest covering the whole liver were drawn on primary staging portal-phase CT. In addition, each liver segment was delineated separately. Mean gray-level intensity, entropy (E), and uniformity (U) were derived with different filters (σ0.5-2.5). Patients/segments without metastases and patients/segments that later developed metachronous metastases were compared using independent samples t tests. RESULTS: Absolute differences in entropy and uniformity between the group without metastases and the group with metachronous metastases group were consistently smaller for the segmental approach compared to the whole-liver approach. No statistically significant differences were found in the texture measurements between both groups. CONCLUSIONS: In this small patient cohort, we could not demonstrate a clear predictive value to identify patients at risk of developing metachronous metastases within 2 years. Segmental CT texture analysis of the liver probably has no additional benefit over whole-liver texture analysis.