DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases.

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

IgA vasculitis following COVID-19 vaccination.

Immunoglobulin A (IgA) vasculitis is generally triggered by infectious causes, but it has also been reported after immunisation with various vaccines. Herein, we report two cases of IgA vasculitis after receiving the first or second dose of the Pfizer-BioNTech BNT16B2b2 mRNA vaccine. Two men, aged 22 and 30 years, developed palpable purpura on the extremities and arthritis. One patient also complained of fever and gastrointestinal symptoms. Laboratory findings revealed mild leucocytosis and slightly elevated C-reactive protein levels, although the platelet count and coagulation profile were within normal levels in both cases. Proteinuria and microhaematuria were seen in one patient. Skin biopsies were performed in both patients and revealed leucocytoclastic vasculitis. The deposits of IgA and C3 were shown in immunofluorescence studies in one patient. Both patients were diagnosed with IgA vasculitis and treated with prednisolone, and their symptoms resolved within 1 week after initiation of treatment. The coronavirus disease 2019 mRNA vaccine could trigger IgA vasculitis; however, a coincidence cannot be ruled out.

Early Recognition and Treatment of Relapsing Polychondritis.

We describe the case of a 60-year-old Japanese man with relapsing polychondritis (RP). The patient was referred to Hamanomachi Hospital due to mild elevation of C-reactive protein and mild anemia on medical checkup without any symptoms. Body CT imaging showed thickened tracheal and bronchial walls with no active lesions in the lung. Precise physical examination revealed swelling in both ears. Bronchoscopy revealed redness and swelling of the tracheal and bronchial mucosa in the membranous lesion. Histologic examination of the bronchial biopsy showed inflammatory cell infiltration in the sub-mucosa with no vasculitis. Serum anti-type 2 collagen antibodies were found to be positive (33.9 EU/mL). Corticosteroid treatment improved his tracheochondritis. It is challenging to diagnose RP in the early stage due to its rarity and nonspecific symptoms. Airway involvement in RP is irreversible and the major cause of morbidity and mortality; hence, early recognition of airway involvement and treatment is warranted.

Intracholecystic papillary neoplasm associated with invasive carcinoma of the remnant gallbladder after subtotal cholecystectomy: a case report.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) of the gallbladder is a rare tumor and a relatively new concept. Therefore, the natural history and imaging characteristics of ICPN have not yet been fully documented. Moreover, cases who underwent curative resection for remnant gallbladder cancer, including ICPN with associated invasive carcinoma, have been rarely reported. We report a resected case of ICPN of the remnant gallbladder with associated invasive carcinoma for which we could observe a temporal change in imaging findings until malignant transformation. CASE PRESENTATION: A 79-year-old female patient with a surgical history of subtotal cholecystectomy for acute cholecystitis was an ambulatory patient of our institution because of postoperative surveillance for colon cancer. Ultrasonography and computed tomography incidentally detected a small nodule in the cystic remnant gallbladder. The nodule had increased in size 3 months later; thus, additional investigations were performed. Magnetic resonance imaging revealed a 10-mm enhanced nodule without evidence of extraluminal invasion. Diffusion-weighted magnetic resonance imaging revealed restricted diffusion of the lesion, and positron emission tomography revealed marked accumulation in the lesion. The lesion was diagnosed as suspicious for a malignant remnant gallbladder tumor. Therefore, remnant cholecystectomy with gallbladder bed resection was performed. Because preoperative endoscopic retrograde cholangiography revealed a relatively long intact cystic duct, extrahepatic bile duct resection was planned to be omitted. Intraoperatively, the hepatic and duodenal side bile duct where the cystic duct diverged was taped. Using these tapes, which permitted pulling the bile duct, the cystic duct located behind the bile duct could be safely exposed. The lesion was pathologically diagnosed as biliary morphologic ICPN with associated invasive carcinoma. CONCLUSIONS: Because remnant cholecystectomy is an uncommon procedure and technically difficult, accurate preoperative investigation and surgical planning are important to prevent bile duct injury and omit extrahepatic bile duct resection. In the present case, intracystic change could be detected incidentally at an early stage because of previous remnant gallbladder producing (reconstituting) subtotal cholecystectomy and surveillance for other disease. This case suggests the existence of ICPN that can progress to invasive carcinoma during a short period.

Idiopathic Pulmonary Fibrosis Complicated by Adenocarcinoma and Organizing Pneumonia.

We describe a case of a 77-year-old male with idiopathic pulmonary fibrosis (IPF) complicated by lung adenocarcinoma and organizing pneumonia (OP). On initial examination, physical examination revealed fine crackles in both sides of his chest. There were no physical findings suggestive of collagen disease. Blood tests showed no elevation of C-reactive protein, and lactate dehydrogenase and Krebs von den Lungen-6 (KL-6) were within normal limits. A high-resolution CT (HRCT) of the chest showed multiple ground-glass opacities (GGOs) in both lungs, with consolidation and traction bronchiectasis in the left lower lobe. Although a bronchoscopy was performed, no diagnosis could be made. Bronchoalveolar lavage showed elevated lymphocytes, and treatment with prednisolone was started for the possibility of OP. Subsequent chest X-ray and chest CT showed worsening of the shadows over time, and shortness of breath on exertion progressed. Surgical lung biopsy revealed IPF complicated by adenocarcinoma and OP. Although the patient was treated with pemetrexed and carboplatin combination therapy, respiratory failure progressed, and palliative care was decided. There is no report of IPF complicated by adenocarcinoma and OP, and early surgical lung biopsy may be important for diagnosis.

A Refractory, Infected Lung Bulla and an Abscess Treated Using Percutaneous Drainage in a Patient With Human T-Lymphotropic Virus Type 1-Associated Myelopathy.

We present a case of a 54-year-old Japanese woman with established human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy who developed a refractory infected lung bulla and lung abscess caused by Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, and Aspergillusspecies. Since antibiotic treatment alone failed to resolve the infection, percutaneous drainage of the infected bulla was performed. Although a prolonged treatment period was necessary, the infected lung bulla and the lung abscess were eventually resolved. During her illness, the patient also developed arthritis, possibly related to the HTLV-1 infection. Thus, persons infected with HTLV-1 can develop refractory infections, myelopathy, and arthritis. Percutaneous drainage is an option to treat refractory infected lung bullae.

Pulmonary tumor embolism from breast cancer diagnosed by selective aspiration cytology using a Swan-Ganz catheter.

We describe a case of pulmonary tumor embolism (PTE) from breast cancer diagnosed by selective aspiration cytology using a Swan-Ganz catheter. A 60-year-old woman was referred to Hamanomachi Hospital because of increased levels of tumor markers. The patient complained only of slight exertional dyspnea and a dry cough. Due to breast cancer, she had undergone a mastectomy followed by radiation and chemotherapy one year earlier. Positron emission tomography scanning with CT images revealed no evidence of malignancy. Repeated chest CT images showed emerging wedge-shaped nodules in the subpleural zones of the left lower lobe with diffuse ground-glass opacities in the bilateral lower lobes. The D-dimer level was negative. Pulmonary perfusion scintigraphy showed multiple small wedge-shaped defect areas on the peripheral sides of the bilateral lungs. Suspecting PTE, we performed selective aspiration cytology from the left pulmonary arteries. Cancer cells were detected from selected branches of left A8 and A9. Morphology and immunostaining led to a final diagnosis of PTE of recurrent breast cancer. Pulmonary embolism of cancer is a progressive, fatal condition with challenging diagnosis. Selective aspiration cytology with a Swan-Ganz catheter is a useful, less invasive option in patients with suspected PTE.

Lenvatinib for poorly differentiated carcinoma of the anterior mediastinum.

We describe a Case of a 74-year-old Japanese man with poorly differentiated carcinoma of the anterior mediastinum. The patient underwent anterior mediastinal tumor resection through median sternotomy. The tumor, 7.0 × 5.0 cm, had invaded surrounding tissues (pericardium, right lung, right and left brachiocephalic veins, and superior vena cava). Complete resection of the tumor was not performed. One month after the operation, the patient developed multiple pulmonary metastases, right pleural dissemination, and carcinomatous pleurisy. He was treated with lenvatinib, a novel multi-kinase inhibitor, to which the metastasis responded favorably. This case reports for the first time the clinical usefulness of lenvatinib for poorly differentiated carcinoma of the anterior mediastinum. Management of side effects by several methods, including suspending use of medication on weekends (called a weekends-off strategy), is another strong argument to continue lenvatinib administration.

Pulmonary amyloidosis complicated with pulmonary hemosiderosis, diagnosed with bronchoscopy.

We describe a case of an 82-year-old Japanese woman with pulmonary amyloidosis and hemosiderosis associated with multiple myeloma. She had a background of end-stage renal failure of unknown etiology and had been on maintenance dialysis for 2 years. She complained of exertional dyspnea for four months. High-resolution CT of the chest revealed diffuse ground-glass opacities with mosaic attenuation, consolidation in the left lingular lobe, and wedge-shaped, subpleural nodules in the bilateral lower lobes. A transbronchial lung biopsy of the left lingular lobe showed deposition of amorphous, eosinophilic amyloid at the smooth muscle layer of bronchial tissue, with a positive Congo red staining signal in polarized light. Bronchoalveolar lavage fluid was brownish-yellow, and numerous hemosiderin-laden macrophages were detected with Berlin blue staining. From these findings, a diagnosis of pulmonary amyloidosis complicated with pulmonary hemosiderosis was made. Further work-up led to a diagnosis of multiple myeloma. Pulmonary amyloidosis complicated with pulmonary hemosiderosis is a rare disorder and may be underdiagnosed. Physical examination, such as the appearance of the tongue, can assist the diagnosis of systemic amyloidosis. Use of bronchoscopy allows physicians make an early diagnosis of pulmonary amyloidosis that is minimally invasive.

Clinicopathologic Significance of EGFR Mutation and HPV Infection in Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma-related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma-related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in situ hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non-ISP-SCCs (P<0.0001). The majority of EGFR mutations were exon 20 insertions, with the remainder composed of deletions and single-nucleotide substitutions in exons 19 and 20. All of 142 SNSCCs harbored no KRAS mutation. EGFR CNG was detected in 41 (28.1%) of 146 SNSCCs; all of them were HPV negative and 3 had EGFR mutations. Collectively, EGFR mutation, EGFR CNG, and HR-HPV were essentially mutually exclusive, and each subgroup had distinct clinicopathologic features. The HPV-negative/EGFR-mutant group, the HPV-negative/EGFR CNG-positive group, and the triple-negative group had significantly worse prognoses than the HPV-positive group (P=0.0265, 0.0264, and 0.0394, respectively). In conclusion, EGFR mutation may play a pathogenetically important role in some populations of SNSCCs, especially ISP-SCCs. The molecular subclassification of SNSCCs may contribute to prognostic prediction and molecular-targeted precision medicine.

Numerous lymph node metastases in early gastric cancer without preoperatively enlarged lymph nodes: a case report.

BACKGROUND: According to the 2018 Japanese gastric cancer treatment guidelines (ver. 5), a reduced extent of lymphadenectomy (D1 or D1+) is indicated for cT1 N0 tumors that do not meet the criteria for endoscopic resection. However, early gastric cancer with multiple lymph node metastases is not unknown, and cases have been reported. We report a case of a patient with early gastric cancer and numerous nodal metastases who underwent laparoscopic proximal gastrectomy based on a preoperative diagnosis of T1 N0. CASE PRESENTATION: A 69-year-old woman underwent emergent endoscopic hemostasis for massive hematemesis of the stomach, and endoscopic examination showed ulceration with a visible vessel. Pathological biopsy examination of the ulcer identified poorly differentiated adenocarcinoma with signet ring cells. The patient was diagnosed with early gastric cancer that was not indicated for endoscopic resection because of the ulceration and histological type. Endoscopic ultrasound showed that the third layer was poorly demarcated at the ulcer scar, indicating invasion to the submucosal layer. Computed tomography did not reveal enlarged lymph nodes or distant metastasis. The preoperative diagnosis was early gastric cancer of the fundus without nodal metastasis, and laparoscopic proximal gastrectomy with D1+ lymphadenectomy was performed. The initial postoperative pathological diagnosis was intramucosal carcinoma without lymphovascular invasion; however, the presence of 26 lymph node metastases was revealed unexpectedly. Additional pathological examination of more resected specimens transected every 2-3 mm revealed that only one lesion contained a small number of cancer cells in the lymphatic duct below the muscularis mucosa. CONCLUSIONS: We report a case of early gastric cancer with 26 nodal metastases in which lymph node involvement was not identified prior to surgery. These findings indicate that the extent of lymphadenectomy and the surgical procedure should be carefully decided even in cT1 N0 early gastric cancer when several risk factors for lymph node metastasis are present.