A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5–10% of tumors at risk for progression. Validation studies failed to ...demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with three-tiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (
n
= 42), an Italian cohort (
n
= 103), a German cohort (
n
= 54), a Japanese cohort (
n
= 119), and The Cancer Genome Atlas cohort (
n
= 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff’s alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (
n
= 382). pT stage, patient’s age (> 65 vs ≤ 65), lymph node and/or distant metastasis, and the two-tiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multi-institutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.
To determine the constituents and origin of the yellow pigment in surgically removed lamellar hole-associated epiretinal proliferation (LHEP) in patients with lamellar macular hole (LMH).
This ...prospective case series comprised nine eyes with LMH in patients aged 41 to 83 years. The presence of LHEP was confirmed by preoperative optical coherence tomography; the distribution of macular pigment was observed by two-wavelength fundus autofluorescence technique before and after surgery. The subjects underwent a 25-gauge vitrectomy, and the surgically removed epiretinal membranous tissue was fixed with formalin. The specimens were examined using resonance Raman microscopy, and paraffin sections were stained with antiglial fibrillary acidic protein.
Seven cases presented with LHEP, and the presence of yellow pigment was confirmed using an operating microscope. Carotenoid-specific Raman signals with three major Raman peaks could be identified in the specimens with LHEP. These specimens were positive for glial fibrillary acidic protein staining. Using the fundus autofluorescence technique, a central defect in the distribution of the macular pigment was noted in the exact area of the lamellar hole. This type of defect was no longer visible after surgical repair of the lamellar hole.
The constituents of the yellow pigment in the removed LHEP were carotenoids that typically originate from the macular xanthophyll pigments at the fovea. Since LHEP is reported to be composed of Müller cells, we hypothesize that xanthophyll carotenoids at the fovea are contained in the Müller cells.
Background
Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer in Japan. Pathological evaluation of ESD specimens is considered essential to determine if ...additional gastrectomy is necessary. Usually, specimens resected by ESD are sliced into 2–3 mm wide sections, and each section is examined for depth of tumor and lymphovascular invasion. Nevertheless, in most cases of additional gastrectomy, lymph node metastasis is not present. Given that there are few-studies on how clinical-decisions based on the pathologic-evaluation-method, in particular the specimen cut-width, influence patient outcomes, we retrospectively evaluated whether reducing the number of cuts to one-half or one-third would result in underestimation of the real need for additional surgery. The effect of the actual cut-width on recommended treatment (referral to operation) and patient-outcomes was also assessed.
Methods
Pathological records of 498 lesions from 439 patients were reviewed and re-evaluated. All pathological descriptions are based on the gastric cancer classification system of the Japanese Gastric Cancer Association, 15th edition.
Results
In 5.8% and 8.5% of the total specimens, underdiagnosis of tumor-depth and lymphovascular invasion occurred when the number of sections was reduced to one-half and one-third, respectively. Significantly more submucosal invasions were found in the group in which the cut-with was between 3 and 4 mm than in the group in which the cut width was less than 3 mm.
Conclusion
Evaluation of the appropriate cut-width is important and should be discussed from the standpoint of labor costs and lost opportunities to search for molecular markers in ESD materials.
Objective
Coatomer subunit alpha (COPA) syndrome, also known as autoinflammatory interstitial lung, joint, and kidney disease, is caused by heterozygous mutations in COPA. We identified a novel COPA ...variant in 4 patients in one family. We undertook this study to elucidate whether and how the variant causes manifestations of COPA syndrome by studying these 4 patients and by analyzing results from a gene‐targeted mouse model.
Methods
We performed whole‐exome sequencing in 7 family members and measured the type I interferon (IFN) signature of the peripheral blood cells. We analyzed the effects of COPA variants in in vitro experiments and in Copa mutant mice that were generated.
Results
We identified a heterozygous variant of COPA (c.725T>G, p.Val242Gly) in the 4 affected members of the family. The IFN score was high in the members carrying the variant. In vitro analysis revealed that COPA V242G, as well as the previously reported disease‐causing variants, augmented stimulator of interferon genes (STING)–induced type I IFN promoter activities. CopaV242G/+ mice manifested interstitial lung disease and STING‐dependent elevation of IFN‐stimulated gene expression. In CopaV242G/+ dendritic cells, the STING pathway was not constitutively activated but was hyperactivated upon stimulation, leading to increased type I IFN production.
Conclusion
V242G, a novel COPA variant, was found in 4 patients from one family. In gene‐targeted mice with the V242G variant, interstitial lung disease was recapitulated and augmented responses of the STING pathway, leading to an increase in type I IFN production, were demonstrated.
Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The current study ...was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma. A total of 60 patients, who were surgically treated for primary ovarian clear cell adenocarcinoma, were enrolled. Surgical specimens were examined for ARID1A protein expression by immunohistochemistry. The correlations between the loss of ARID1A expression and clinicopathological characteristics, prognosis, and chemosensitivity were investigated. Loss of ARID1A expression was identified in 9 (15.0%) of 60 ovarian clear cell carcinoma samples. Loss of ARID1A staining intensity (0+) was more frequently found in cells of clear cell carcinomas than in high-grade serous carcinomas (P<0.01). Loss of ARID1A expression was significantly correlated with advanced FIGO stage and high CA125 levels (P=0.02, 0.01). There were no significant correlations between loss of ARID1A expression and patient age, status of residual tumor, Ki-67 labeling index, or the status of endometriosis. Loss of ARID1A correlated with shorter progression-free survival of patients with clear cell carcinomas treated with platinum-based chemotherapy (P<0.01). Loss of ARID1A expression tended to correlate with shorter overall survival in patients with ovarian clear cell carcinomas treated with platinum-based chemotherapy. When data were stratified for the multivariate analysis, only the loss of ARID1A expression remained a significant (P=0.03) predictor of reduced progression-free survival. Of the 60 patients with ovarian clear cell carcinomas, 14 patients had measurable residual tumor after primary cytoreductive surgery. Tumors with loss of ARID1A expression were more likely to be chemoresistant than tumors with positive ARID1A expression (100.0 vs 40.0%, P=0.04). This study demonstrates that loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy. Measurement of ARID1A expression may be a method to predict resistance to platinum-based chemotherapy in patients with ovarian clear cell carcinoma.
A 71-year-old man was admitted for left-sided chest pain. He had a history of diabetes, treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small-cell lung ...cancer, and corticosteroid treatment for underlying lung diseases. Chest computed tomography showed consolidations in the bilateral lower lobes, and Aspergillus fumigatus was detected by bronchoscopy. Invasive pulmonary aspergillosis was suspected, and antifungal therapy with voriconazole was initiated; however, the patient passed away suddenly. Autopsy revealed disseminated Aspergillus infection and intra-abdominal hemorrhage due to the rupture of a splenic vein aneurysm caused by Aspergillus necrotizing vasculitis, which was considered the cause of death.
Abstract
Previous studies have largely failed to clarify the relationship between p16
INK4A
status and cervical adenocarcinoma prognosis. The current study aimed to examine the clinical and ...pathological significance of p16
INK4A
expression in several cervical adenocarcinoma subtypes. Eighty-two samples collected from patients with cervical adenocarcinoma were formalin fixed and paraffin embedded. Next, p16
INK4A
levels were analyzed with immunohistochemistry. Additionally, the relationship between p16
INK4A
expression and clinicopathological factors as well as prognosis was evaluated. The expression of p16
INK4A
was mostly detected in all usual cervical adenocarcinoma subtypes. In the gastric type, only a few cases were positive for p16
INK4A
expression. Results of the Kaplan–Meier analysis indicated that the positive p16
INK4A
expression in tumor cells was significantly associated with favorable progression-free survival and overall survival in patients with cervical adenocarcinoma (
p
= 0.018 and
p
= 0.047, respectively, log-rank test). Our findings suggest that the status of p16
INK4A
expression may influence prognosis. Thus, p16
INK4A
expression could be used as a biomarker for improving the prognosis of patients with cervical adenocarcinoma.
Background
Primary pulmonary meningiomas (PPMs) are a rare mostly benign disease presenting as a solitary pulmonary nodule and are hardly distinguishable from a metastatic tumor because of a lack of ...specific radiological features. We described a case of a PPM initially diagnosed as a metastatic lung tumor from thyroid cancer with a size reduction after radioactive iodine therapy.
Case presentation
A 62-year-old woman who had undergone a total thyroidectomy for a papillary thyroid carcinoma 6 years prior presented with an enlarging pulmonary nodule. The nodule had decreased in size from 7.0 to 5.5 mm after adjuvant radioactive iodine therapy and enlarged to 8.7 mm over the next 5 years. Under a clinical diagnosis of a metastatic lung tumor, she underwent a thoracoscopic pulmonary wedge resection and was pathologically diagnosed with a PPM.
Conclusion
A surgical resection is required for histological diagnoses of PPMs especially in patients with a history of a malignancy.
Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade ...3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (
= 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (
= 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.
Background
A solitary pulmonary nodule (SPN) poses a diagnostic challenge, which includes both a benign and malignant etiology. A size enlargement often indicates malignancy. We herein describe a ...case of a solitary pulmonary metastasis from a leiomyosarcoma that regressed transiently during follow-up.
Case presentation
A 47-year-old woman presented with an SPN detected by follow-up computed tomography 7 years after surgery for a left forearm high-grade leiomyosarcoma. The nodule regressed spontaneously after an additional 6 months, and therefore, an inflammatory change was the most likely diagnosis at that time. However, the nodule enlarged again over the next 5 years. The growth rate led us to suspect a malignancy. A trans-bronchial biopsy was undiagnostic and a video-assisted thoracic surgery was planned. She underwent a wedge resection of the right lung, and a histopathological examination found it was a metastatic leiomyosarcoma.
Conclusions
A pulmonary metastasis from a leiomyosarcoma could emerge as an SPN and reveal a subsequent transient size reduction. An SPN in patients even with a remote history of a soft tissue tumor should raise the possibility of metastasis, and periodic follow-up is essential even after the size reduction.
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