A New Indicator to Differentiate Thyroid Follicular Inclusions in Cervical Lymph Nodes from Patients with Thyroid Cancer.

Nodal metastasis is crucial for determining the stage of well-differentiated thyroid cancer (WTC) in patients older than 55. Well-formed thyroid follicular inclusions (TFIs) are occasionally encountered in the cervical lymph nodes (LNs) of patients with papillary thyroid carcinoma (PTC), and it is difficult to determine whether they are true nodal metastases or ectopic thyroid tissues (ETT). This study aimed to elucidate the impact of the expression of the DNA damage response molecule TP53-binding protein 1 (53BP1) using immunofluorescence (IF) as a biomarker to differentiate TFIs in cervical LN by comparing the mutation analyses of primary thyroid cancers. The data demonstrated the necessity for the differential diagnosis of true metastases from ETT among TFIs in cervical LNs. PTC-like nuclear features using hematoxylin-eosin staining combined with immunohistochemistry for conventional biomarkers of PTC, including BRAFV600E protein, were most helpful in identifying metastatic follicular-patterned carcinomas. In conclusion, IF analysis of 53BP1 expression could be an excellent ancillary technique to distinguish metastatic carcinoma or ETT from TFIs in LNs, particularly in cases other than BRAFV600E-mutated PTC.

Cervical Superficially Invasive Squamous Cell Carcinoma With Supraclavicular Lymph Node Metastasis: A Case Report.

Typically, local spread and lymph-vascular space invasion (LVSI) occur before lymph node (LN) and distant metastases during the progression of uterine cervical cancer. The prognostic value of LVSI in cervical superficially invasive squamous cell carcinoma (SISCC) is still debated. We encountered a rare case of cervical SISCC without LVSI presenting with multiple LN metastases, including pelvic, para-aortic, and left supraclavicular LNs. Immunohistochemical analysis of p16 and in situ hybridization of human papillomavirus confirmed the relationship of the cervical SISCC and pelvic LN metastases. Aspiration cytology of the left supraclavicular LN showed squamous cell carcinoma and our final diagnosis was uterine cervical squamous cell carcinoma, stage IVB. The patient underwent adjuvant chemotherapy. Although relapse was observed at the vaginal stump and in pelvic and para-aortic LNs, chemotherapy and radiotherapy were effective. The patient is alive without disease 40 mo after initial treatment. This is the first case report of cervical SISCC without LVSI presenting with supraclavicular LN metastasis, which contributes to our understanding of the value of LVSI. Immunohistochemical analysis of p16 and in situ hybridization of human papillomavirus were useful in confirming the relationship of cervical SISCC and its metastases. As cervical SISCC with LN metastasis is rare, multi-institutional joint research is needed to clarify its prognosis and appropriate treatment.

Esophageal metastasis of renal cell carcinoma resected by endoscopic submucosal dissection: a case report.

BACKGROUND: Esophageal metastasis of renal cell carcinoma (RCC) is extremely rare. We have described herein a case of a 59-year-old man with esophageal metastasis of RCC that was endoscopically resected. CASE PRESENTATION: The case was a 59-year-old man who had undergone left nephrectomy for renal clear cell carcinoma 17 years ago and splenectomy for splenic metastasis 3 years ago. Esophagogastroduodenoscopy (EGD) performed 9 years ago revealed a small reddish elevated lesion with a smooth surface in the middle esophagus; this lesion increased in size 4 years ago. However, no biopsy was performed. The lesion continued to grow in size and was found to have become nodular during the present observation. Biopsy revealed clear cell carcinoma. Endoscopic ultrasound (EUS) revealed that the lesion had not invaded the submucosa, and contrast-enhanced computed tomography did not reveal any other metastasis. The lesion was successfully removed en bloc via endoscopic submucosal dissection (ESD). Pathologically, the tumor was detected in the subepithelium with focal infiltration of the muscularis mucosa. It consisted of monotonous cells with small nuclei and a clear cytoplasm. Immunohistological findings indicated that the tumor was a metastasis of RCC. The lateral and vertical margins were noted to be free. CONCLUSIONS: We have presented herein a case of esophageal metastasis of RCC that had progressed over 9 years and was then resected en bloc through endoscopic submucosal dissection.

[Falx Meningioma Presenting with Intratumoral Hemorrhage and Interhemispheric Acute Subdural Hematoma:A Case of Report].

A 68-year-old male with a sudden headache while defecation was transferred to our hospital. He was initially diagnosed with intracerebral hemorrhage in the right occipital lobe and acute subdural hematoma(ASDH)in the right interhemispheric fissure. A CT angiography(CTA)showed stenosis in the superior sagittal sinus(SSS)and the vein of Galen(VG)near the hematoma, which were considered to be due to compression of the hematoma. In the source image of CTA, the enhancement effect of the hematoma part was not clear. MRI revealed a heterogeneous mixed signal intensity in the hematoma area, suggesting a mixture of hematoma components that had bled at different times. Cerebral angiography performed two weeks after onset showed a tumor shadow imaged from the middle meningeal artery. Therefore, the presence of hemorrhagic meningioma was suspected. This was confirmed by contrast-enhanced MRI. One month after the onset, tumor resection was performed after the embolization of the feeding artery. Part of the tumor around the SSS and VG was left due to severe adhesion. Postoperatively, stenosis of the SSS and VG significantly improved. In this case, the increase in venous pressure may be related to the bleeding mechanism. Hemorrhagic onset meningioma with interhemispheric ASDH is extremely rare, and only 4 cases have been reported. It is easy to misdiagnose if only non-contrast CT is used. It should be noted that in cases of intratumoral hemorrhage, CTA may not show an enhancing effect in the acute phase. Since contrast-enhanced MRI may be useful for a definitive diagnosis, it should be performed at the time of initial imaging.

Steroid-resistant protein-losing gastroenteropathy complicated with Sjögren's syndrome successfully treated with mizoribine.

A 64-year-old woman with leg edema was diagnosed with protein-losing gastroenteropathy and Sjögren's syndrome. Central venous nutrition led to infection of her catheter, ascites, and deep vein thrombosis. Following successful treatment of these conditions with antibiotics and anticoagulants, she was treated unsuccessfully with prednisolone and steroid pulse therapy. Mizoribine add-on markedly reduced edema and normalized serum albumin. This is the first report of a steroid-resistant protein-losing gastroenteropathy patient with Sjögren's syndrome successfully treated with mizoribine.

[Hypoplastic acute promyelocytic leukemia with continuous hypocellular bone marrow after remission].

An 87-year old female presented with unsteady gait and occasional subcutaneous hematomas. Blood examination findings revealed pancytopenia and mild coagulopathy. Both the histopathological evaluation of bone marrow smears and bone marrow biopsy revealed a hypocellular bone marrow. However, APL cells were observed and PML-RARA fusion gene was detected. On the basis of these findings, the patient was diagnosed with hypoplastic acute promyelocytic leukemia. She received ATRA treatment and achieved complete remission (CR) 29 days from the commencement of therapy. After the first CR, she received two courses of ATO as a consolidation therapy. Following the latter treatments, she maintained CR, but a hypoplastic bone marrow was still observed. Hypoplastic AML is defined as AML with a low bone marrow cellularity. It is clinically important to distinguish it from aplastic anemia and hypoplastic MDS. It has been suggested that both cytogenetic and morphological diagnosis are imperative to the differential diagnosis of hypocellular bone marrow.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) producing large cell neuroendocrine carcinoma (LCNEC) of lung with multiple liver metastases: A case report.

A 78-year-old man was admitted to our hospital for multiple lung and liver tumors. Initial clinical diagnosis was hepatocellular carcinoma (HCC) with lung metastases because of a high value of serum protein induced by vitamin K absence or antagonist II (PIVKA-II) (6,705 mAU/mL). However, a review of a prior CT showed the lung tumor had existed 6 months before liver tumors were detected. The tumors progressed rapidly and the patient died 37 days after admission. Autopsy revealed that both lung and liver tumors exhibited the histology of large cell neuroendocrine carcinoma (LCNEC). Immunohistochemistry revealed that the tumor cells expressed not only neuroendocrine markers but also PIVKA-II diffusely. Hepatoid differentiation was not detected. Background liver did not show any chronic liver disease. The final diagnosis was PIVKA-II producing LCNEC of the lung with multiple liver metastases. PIVKA-II producing tumors other than HCC are extremely rare. To our best knowledge, this is the first case report of PIVKA-II producing neuroendocrine tumors of the lung.

Multicentric Castleman disease mimicking IgG4-related disease: A case report.

A 50-year-old woman was referred to our hospital for shoulder joint stiffness. She had a history of polyclonal hypergammaglobulinemia and an elevated C-reactive protein level. Her laboratory data revealed an elevated serum immunoglobulin G4 (IgG4) level, hypergammaglobulinemia, and rheumatoid factor positivity in the absence of anticyclic citrullinated peptide antibody. [18F]-Fluorodeoxyglucose positron emission tomography showed significant [18F]-fluorodeoxyglucose uptake in multiple lymph nodes (axillary, hilar, para-aortic, and inguinal). Biopsy of the inguinal lymph node showed expansion of the interfollicular areas by heavily infiltrating plasma cells, consistent with multicentric Castleman disease (MCD). Immunohistochemical analysis revealed a 37.3% IgG4-positive:IgG-positive plasma cell ratio, indicating overlapping IgG4-related disease. However, serological cytokine analysis revealed elevated levels of interleukin-6 (9.3 pg/ml) and vascular endothelial growth factor (VEGF) (1210 pg/ml), which are compatible with MCD. Corticosteroid treatment resolved the serological and imaging abnormalities. IgG4-related disease can mimic MCD, and it is crucial to distinguish between these two diseases. Serum interleukin-6 and VEGF levels may help to discriminate MCD from IgG4-related disease.

Low Expression of S100P Is Associated With Poor Prognosis in Patients With Clear Cell Adenocarcinoma of the Ovary.

OBJECTIVE: The S100P protein stimulates cell proliferation and survival, thereby contributing to cancer progression. The purposes of this study were to evaluate S100P expression in ovarian clear cell adenocarcinoma and to determine whether S100P expression was correlated with the clinicopathological features or prognoses of patients with clear cell adenocarcinoma. METHODS: We examined S100P expression in 30 ovarian clear cell adenocarcinoma specimens using immunohistochemistry analysis. The Kaplan-Meier method was used for analysis of overall survival, and comparisons were made based on the log-rank test. RESULTS: Negative staining for nuclear S100P was associated with a poor prognosis as compared with that of positive staining for nuclear S100P in specimens from patients with clear cell adenocarcinoma. CONCLUSIONS: These data suggested that S100P may serve as an independent prognostic factor and marker for acquired resistance to chemotherapeutic drugs in clear cell adenocarcinoma.

Amyloid Deposition Mainly Localized in the Basal Area of the Left Ventricle in a Patient with Amyloid Transthyretin Cardiac Amyloidosis.

A 74-year-old Japanese man was admitted to our hospital for catheter ablation of paroxysmal atrial fibrillation. Transthoracic echocardiography revealed basal interventricular septal hypertrophy without apical sparing. Cardiac magnetic resonance imaging revealed late gadolinium enhancement in the hypertrophic lesions. The Kumamoto criteria was one point, and the patient had no carpal tunnel syndrome. However, technetium-99m pyrophosphate scintigraphy revealed an accumulation in the basal region of the left ventricle. A skin biopsy revealed transthyretin (TTR) amyloid deposition. A TTR gene examination revealed no variants. This case suggests that amyloid deposition in TTR may occur in the basal area of the interventricular septum.

Sarcomatoid renal cell carcinoma with an inferior vena cava tumor thrombus that was completely resected by robot-assisted laparoscopic radical nephrectomy after neoadjuvant therapy nivolumab plus ipilimumab: a case report.

We here present a patient with a sarcomatoid renal cell carcinoma complicated by inferior vena cava tumor thrombus that we treated with nivolumab plus ipilimumab. This resulted in shrinkage of the tumor, enabling complete resection by robot-assisted laparoscopic radical nephrectomy. The patient is still alive with no evidence of recurrence.

Epstein-Barr virus and methotrexate-related CNS lymphoma in a patient with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA), especially those treated with methotrexate (MTX), might have an increased risk of lymphoproliferative disorders that are associated with Epstein-Barr virus (EBV). We describe a case of EBV-associated central nervous system (CNS) lymphoma (diffuse large B-cell lymphoma) in a patient with RA on a short course of MTX treatment. The neoplastic cells express the B-cell surface markers (CD20, Pax-5 and CD30), and EBV-encoded RNA was demonstrated by in situ hybridization. The patient's lymphoma did not recur for the 8-year follow-up period after the tumor resection and cessation of MTX. MTX may promote EBV-positive CNS lymphoma in RA patient due to its immunosuppressive properties as well as reactivating latent EBV infection.

Fulminant Myocarditis and Acute Appendicitis after COVID-19 Vaccination.

A 19-year-old Japanese man was hospitalized for cardiogenic shock 28 days after receiving a second dose of the coronavirus disease 2019 (COVID-19) mRNA-1273 vaccine. He had had a high fever for three days with vomiting and abdominal pain before arriving at our hospital. The patient visited a local hospital and was diagnosed with heart failure and acute appendicitis. An endomyocardial biopsy specimen showed myocarditis. Thereafter, Impella CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were initiated immediately along with inotropic support and steroid pulse therapy. Given these findings, he was finally diagnosed with multiple inflammatory syndrome and fulminant myocarditis.

Differentiation Between Heterogeneous GGN and Part-Solid Nodule Using 2 D Grayscale Histogram Analysis of Thin-Section CT Image.

INTRODUCTION/BACKGROUND: To evaluate cases of surgically resected pulmonary adenocarcinoma (Ad) with heterogenous ground-glass nodules (HGGNs) or part-solid nodules (PSNs) and to clarify the differences between them, and between invasive adenocarcinoma (IVA) and minimally invasive adenocarcinoma (MIA) + adenocarcinoma in situ (AIS) using grayscale histogram analysis of thin-section computed tomography (TSCT). MATERIALS AND METHODS: 241 patients with pulmonary Ad were retrospectively classified into HGGNs and PSNs on TSCT by three thoracic radiologists. Sixty HGGNs were classified into 17 IVAs, 26 MIAs, and 17 AISs. 181 PSNs were classified into 114 IVAs, 55 MIAs, and 12 AISs. RESULTS: We found significant differences in area (P = 0.0024), relative size of solid component (P <0.0001), circumference (P <0.0001), mean CT value (P <0.0001), standard deviation of the CT value (P <0.0001), maximum CT value (P <0.0001), skewness (P <0.0001), kurtosis (P <0.0001), and entropy (P <0.0001) between HGGNs and PSNs. In HGGNs, we found significant differences in relative size of solid component (P <0.0001), mean CT value (P = 0.0005), standard deviation of CT value (P = 0.0071), maximum CT value (P = 0.0237), and skewness (P = 0.0027) between IVAs and MIA+AIS lesions. In PSNs, we found significant differences in area (P = 0.0029), relative size of solid component (P = 0.0003), circumference (P = 0.0004), mean CT value (P = 0.0011), skewness (P = 0.0009), and entropy (P = 0.0002) between IVAs and the MIA+AIS lesions. CONCLUSION: Quantitative evaluations using grayscale histogram analysis can clearly distinguish between HGGNs and PSNs, and may be useful for estimating the pathology of such lesions.

Pulmonary Coccidioidomycosis Complicated by Nontuberculous Mycobacterial Pulmonary Diseases with a Literature Review.

Following an endobronchial examination, a young mine supervisor was treated with antibiotics for a pulmonary nontuberculous mycobacterial infection for approximately one year. However, a review of the radiological findings revealed a different possibility. Accordingly, pulmonary resection was performed, and histopathological analysis revealed numerous yeast-like fungi. Since the patient had stayed in the southwestern United States for two months in 2009, eight years previously, coccidioidomycosis was strongly suspected. The diagnosis of coccidioidomycosis was subsequently confirmed by serology and polymerase chain reaction testing of the excised specimen. Here, we report an educational case that emphasizes the importance of meticulous medical history-taking and awareness of endemic mycoses in other countries in the context of globalization.

Fulminant Myocarditis 24 Days after Coronavirus Disease Messenger Ribonucleic Acid Vaccination.

A 60-year-old Japanese woman was hospitalized for cardiogenic shock 24 days after receiving the second dose of the coronavirus disease 2019 BNT162b2 vaccine. Impella CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were immediately initiated along with inotropic support and steroid pulse therapy, as an endomyocardial biopsy specimen showed myocarditis. Three weeks later, her cardiac function had recovered, and she was discharged. An immune response associated with the presence of spike protein in cardiac myocytes may be related to myocarditis in the present case because of positive immunostaining for severe acute respiratory syndrome coronavirus 2 spike protein and C4d in the myocardium.

Molecular Pathological Characteristics of Thyroid Follicular-Patterned Tumors Showing Nodule-in-Nodule Appearance with Poorly Differentiated Component.

Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 (53BP1) is a DNA damage response (DDR) molecule that rapidly localizes at DNA double-strand breaks. Using dual-color immunofluorescence with Ki-67, the profile of 53BP1 expression is shown to be significantly altered during diverse tumorigenesis. In this study, we aimed to elucidate the malignant potential of PDc at the molecular level. We analyzed the profile of 53BP1 expression and NRAS codon 61 and TERT-promoter (TERT-p) mutations in 16 cases of TFTs showing NN with PDc compared to 30 adenomatous goiters, 31 follicular adenomas, 15 minimally invasive follicular carcinomas (FCs), and 11 widely invasive FC cases. Our results revealed that the expression level of abnormal type 53BP1 and incidence of NRAS and TERT-p mutations in PDc were comparable to FCs, suggesting a malignant potential. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations.

Significance of abnormal 53BP1 expression as a novel molecular pathologic parameter of follicular-shaped B-cell lymphoid lesions in human digestive tract.

The digestive tract is a common site of extranodal malignant lymphomas (MLs) and benign lymphoid lesions (BLs). TP53-binding protein 1 (53BP1) expression has been widely investigated in class switch recombination but rarely in human lymphoid tissues with respect to tumorigenesis. We previously reported that immunofluorescence (IF) analysis of 53BP1 nuclear foci (NF), reflecting DNA double strand breaks, is useful for estimating genomic instability in different tumor types. In this study, we evaluated the potential of IF-based analysis of 53BP1 expression in differentiating MLs from BLs. We examined 231 biopsied tissue samples of primary MLs and BLs in the digestive tract. The 53BP1 immunoreactivity pattern was determined by multicolor IF. Compared to BLs, MLs showed a high frequency of abnormal 53BP1 expression (p < 0.0001). Statistically, abnormal 53BP1 expression is an effective test for distinguishing follicular lymphomas from BLs (specificity 98.6%, sensitivity 86.8%) and for distinguishing small B-cell lymphomas from BLs (specificity 98.3%, sensitivity 77.6%). Furthermore, a high frequency of abnormal 53BP1 expression was associated with "high-risk" MALT lymphomas, which exhibited t(11;18)(q21;21) (p = 0.0145). Collectively, these results suggest that IF-based analysis of 53BP1 expression in biopsy samples is a promising technique for diagnosing MLs in the digestive system.

A refractory pleural effusion caused by a pleural capillary hemangioma.

A 69-year-old man presented with a left pleural effusion. Even after repeated drainage, the pleural effusion had been increasing for more than two years. Thoracoscopy unexpectedly showed a pleural mass on the parietal pleura, and it was completely removed. The diagnosis was pleural capillary hemangioma, and the effusion has not recurred after the resection. Pleural hemangioma is one of the crucial differential diagnoses of refractory pleural effusion.

[Nonrecanalization after mechanical thrombectomy in acute ischemic stroke due to infective endocarditis: an autopsy case].

An 86-year-old man was admitted for the abrupt onset of right hemiparesis and aphasia. DWI revealed the high intensity legion in the left insular cortex, and MRA demonstrated the left middle cerebral artery occlusion. Recanalization of the artery was not achieved after mechanical thrombectomy. The diagnosis of infective endocarditis was made as Enterococcus faecalis was cultured from the blood, and mobile vegetation was detected at the aortic valve by transthoracic echocardiography. The patient died from multiple organ failure at 19 days. Autopsy findings revealed fibrin-rich thrombus in the left middle cerebral artery containing neutrophils and bacteria. At the occluded site, neutrophils had intensively infiltrated into the vessel wall, and endothelial cells had partially disappeared. Moreover, disrupted internal elastic lamina was discovered. These findings could indicate that the thrombus had adhered to the vessel wall. The adhesion of the thrombus and vessel wall could be associated with unsuccessful recanalization after endovascular thrombectomy in patients with ischemic stroke due to infective endocarditis.