Pulmonary Tumor Thrombotic Microangiopathy Secondary to Extramammary Paget's Disease: An Autopsy Case Report and Literature Review.

Pulmonary tumor thrombotic microangiopathy is a fatal disease secondary to some malignant tumors, such as gastric cancer, esophageal cancer, and pancreatic cancer. A 61-year-old man presented to our clinic with a red plaque with erosion on his scrotum and was diagnosed with extramammary Paget's disease. Seven years after the initial diagnosis, multiple bone metastases were discovered, and he was started on oral administration of tegafur/gimeracil/oteracil. Two years after beginning the oral drug administration, the patient complained of dyspnea. A chest CT scan showed ground-glass opacity. Pulmonary artery blood cytology revealed carcinoma cells. He was diagnosed with pulmonary tumor thrombotic microangiopathy. At 9 days after the diagnosis, he died of circulatory and respiratory failure. The autopsy revealed microscopic metastatic tumor emboli in multiple pulmonary vessels with fibrin thrombus, which confirmed the earlier cytologic diagnosis. Observations in our case were consistent with the typical pattern of this pathology in the lung with multiple metastases. Pulmonary tumor thrombotic microangiopathy with a primary disease of cutaneous malignancy is extremely rare. Here, we report a rare case of pulmonary tumor thrombotic microangiopathy secondary to extramammary Paget's disease with a literature review.

Safety and tolerability of PD-1/PD-L1 inhibitors in elderly and frail patients with advanced malignancies.

The number of elderly patients with cancer has increased due to aging of the population. However, safety of programmed cell death-1 (PD-1) or programed cell death ligand 1 (PD-L1) inhibitors in elderly patients remains controversial, and limited information exists in frail patients. The present study retrospectively identified 197 patients treated with nivolumab, pembrolizumab or atezolizumab for unresectable advanced cancer between September 2014 and December 2018. Patients were divided into the elderly (age, ≥75 years) and non-elderly (age, <75 years) groups. The detailed immune-related adverse events (irAE) profile and development of critical complications were evaluated. To assess tolerability, the proportion of patients who continued PD-1/PD-L1 inhibitor for >6 months was analyzed. In the two groups, a three-element frailty score, including performance status, Charlson Comorbidity Index and neutrophil-lymphocyte ratio, was estimated, and patients were divided into the low-, intermediate- and high-frailty subgroups. Safety and tolerability were evaluated using the aforementioned items. A total of 58 patients (29.4%) were aged ≥75 years. No significant difference was found in the development of irAEs, hospitalization and treatment discontinuation due to irAEs between the two groups. However, the occurrence of unexpected critical complications was significantly higher in the elderly group (P=0.03). Among the elderly patients with high frailty, more critical complications and fatal irAE (hepatitis) were observed. In this population, 33.3% were able to continue treatment for >6 months without disease progression. The present analysis based on real world data showed similar safety and tolerability of PD-1/PD-L1 inhibitors in elderly patients with advanced malignancies. However, the impact of irAE in elderly patients, especially those with frailty, was occasionally greater compared with that in younger and fit patients.

Acquired agminated melanocytic nevus in the acral area is a potential mimicker of acral lentiginous melanoma: A three-case series report and published work review.

Agminated nevus refers to a clustered group of melanocytic nevi confined to a localized area of the body. It rarely involves acral skin, but recognition of acquired agminated nevus (AAN) in the acral area is clinically important because it may mimic acral lentiginous melanoma (ALM). However, acral AAN has only been described in a few case reports and its clinical characteristics remain unclear. We report three additional cases of acral AAN to further analyze the differential points between ALM. Clinical images, including those of dermoscopy, of three cases of acral AAN were reviewed. The lesions were located on the sole or lateral border of the foot. All acral AAN were flat and large in size (>20 mm in greatest dimension), and associated with asymmetry and irregular border. However, no parallel ridge pattern suggesting ALM was observed on dermoscopy. In two patients, the lesions on the sole were totally resected; microscopic evaluation of these two lesions confirmed junctional nests of banal melanocytes. AAN lesions on the sole with chronic mechanical pressure are slightly larger and more diffuse; thus, they may be more likely to be overdiagnosed as malignancy upon inspection than those in the non-acral area. Understanding the concept of the disease and careful dermoscopic evaluation leads to an accurate diagnosis.

High dose rate interstitial brachytherapy for early stage lip cancer using customized dental spacer.

The present study aimed to report the efficacy and toxicity of our high-dose-rate (HDR) brachytherapy for early stage lip cancer (LC) using customized dental spacers. A retrospective analysis was performed among six patients with early stage LC treated with HDR interstitial brachytherapy between April 2015 and August 2019 using customized dental spacers. The total treatment dose was 49 Gy/7 fractions or 54 Gy/9 fractions. The median follow-up duration for the patients was 13 (range: 2-52) months. All patients completed the entire brachytherapy protocol safely and have experienced no local recurrence thus far. The CTV D100 and D90 values per fraction were median 100 (range: 98.3-100) % prescribed dose (PD) and median 133.4 (range: 129.3-138.9) % PD, respectively. The D2cc and D0.1cc values per fraction for the mandible were median 1.07 (range, 0.79-1.88) Gy and median 1.65 (range: 1.21-2.83) Gy, D2cc and D0.1cc values per fraction for oral cavity were median 1.48 (range, 1.31-1.72) Gy and median 2.73 (range: 1.79-2.88) Gy, respectively. Acute toxicities encountered were mucositis and lip edema limited to the irradiated area; none of them was beyond grade 2 and all were resolved within 1-2 months after treatment. We did not observe any late grade 2 adverse events or worse. This study shows that the adverse effects of HDR brachytherapy for early stage LC can be minimized using a dental spacer. Cooperation with the dentistry department is essential to make spacers that are individually customized for each patient.

Clinical features of immune-related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD-1 blockade.

Programmed cell death protein-1 (PD-1) blockade therapy has improved outcomes in the treatment of advanced cancers. The therapy is well-tolerated, although it occasionally causes immune-related adverse events (irAEs). Thyroid dysfunction is one of the most common irAEs seen. Our aim was to clarify the clinical characteristics of thyroid dysfunction induced by PD-1 blockade and its association with the therapeutic effect of the treatment in advanced cancers. A total of 174 patients who received nivolumab or pembrolizumab for metastatic or unresectable advanced cancers were included in this retrospective study. The patients were divided into two groups: The thyroid dysfunction group and the euthyroid group. In the present study, the clinical characteristics, the association with anti-thyroid antibodies, as well as the progression-free survival (PFS) and overall survival (OS) were estimated. An adjusted Cox proportional hazard regression model was used to evaluate prognostic factors for OS and PFS. This study showed that 25 out of 150 patients (16.7%) developed immune-related thyroid dysfunction. Hypothyroidism occurred in the early stage of the clinical course (median: 12 weeks); subsequently, 9 of the 25 patients underwent a transient period of hyperthyroidism, all with mild symptoms. The presence of positive anti-thyroid antibodies at baseline was significantly higher in the thyroid dysfunction group (13/22) than in the euthyroid group (18/100, P=0.0002). Moreover, PFS (median: 66 vs. 27 weeks, hazard ratio (HR): 0.50, 95% CI: 0.26-0.89, P=0.02) and OS (median 156 vs. 59 weeks, HR: 0.34, 95% CI: 0.13-0.75, P=0.01) were significantly longer in the thyroid dysfunction group than in the euthyroid group. Multivariable analysis also revealed that thyroid dysfunction was an independent prognostic factor for OS (HR: 0.42, 95% CI: 0.16-0.97, P=0.04). These findings may enable the early recognition and appropriate management of thyroid dysfunction, and help in maximizing the therapeutic effect of PD-1 blockade.

Clinical Usefulness of the Platelet-to Lymphocyte Ratio in Patients with Angiosarcoma of the Face and Scalp.

Angiosarcoma of the face and scalp (ASFS) is an extremely aggressive tumor that frequently metastasizes, often leading to death. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are inflammatory markers that predict outcome of various cancers. We aimed to examine the relationship between pretreatment inflammatory markers and ASFS outcome. We included 17 patients with ASFS and a control group of 56 age- and gender-matched healthy individuals. Total white blood counts, neutrophil, lymphocyte, monocyte, and platelet counts were recorded; NLR, PLR, and LMR were calculated. Kaplan-Meier curves were used to calculate overall survival (OS) and distant metastasis-free survival (DMFS). Optimal cut-off values for each inflammatory marker were calculated using receiver operating curve analysis. Median follow-up was 22 months (range, 6-75). There was a statistically significant difference in absolute neutrophil counts and NLR between patient and control groups. Two-year OS and DMFS rates were 41% and 35%, respectively. In patients with tumors < 10 cm, PLR was highly correlated with DMFS, with the 2-year DMFS for those with a high PLR being 50% compared with 100% for those with a low PLR (p = 0.06). This study suggests that PLR is superior to NLR and LMR, and is a clinically useful marker in patients with ASFS with small tumors.

Definitive Radiation Therapy for Angiosarcoma of the Face and Scalp.

AIM: To examine the role of radiation therapy (RT) and factors' influence on tumor control for angiosarcoma of the face and scalp (AS-FS). PATIENTS AND METHODS: We reviewed the records of 14 patients with histopathology proven AS-FS (median age=77 years) who underwent RT between 2000 and 2015. A total dose of 60 to 100 Gy was administered in 24 to 50 fractions. The median calculated biological effective dose (BED) was 93 Gy (range=63.25-120) based on α/ß=10. The median follow-up was 16 months (range=5-62). RESULTS: Of the 14 patients, 8 patients (57%) experienced disease recurrence. The median overall survival (OS) rate was 31 months. The 1-year actuarial OS, event-free survival (EFS) and local control (LC) rates were 83%, 71% and 71%, respectively. In univariate analysis, age ≥78years was a significant prognostic factor for LC and OS. BED ≥95Gy was highly correlated with increased LC with borderline significance (p=0.06). CONCLUSION: Older patients had significantly lower survival rates and higher local recurrence rates than younger patients. The higher radiation dose may have a potential to improve local control for AS-FS.

Malignant melanoma with probable smooth muscle differentiation.

Malignant melanomas occasionally exhibit various divergent differentiation types. Of these, smooth muscle differentiation is extremely rare; only 1 case has been reported in the literature until recently. We report an extremely rare case of malignant melanoma with smooth muscle differentiation, which appeared as an amelanotic reddish nodule on the left toe.