Insulin-like Growth Factor II mRNA-binding Protein 3 is a Highly Sensitive Marker for Intravascular Large B-cell Lymphoma: Immunohistochemical Analysis of 152 Pathology Specimens From 88 Patients.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non-germinal center B cells were detected in only 2 samples ( P = 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.

Fulminant myocarditis with complete atrioventricular block after mRNA COVID-19 vaccination: A case report.

A 71-year-old man was transferred urgently to our hospital after collapsing near his home post the first shot of the BNT162b2 coronavirus disease 2019 vaccine (Pfizer-BioNTech, Comirnaty®). Immediately after arrival at our hospital, cardiac arrest due to complete atrioventricular block with no ventricular escaped beats was observed on electrocardiogram. Echocardiography showed preserved left ventricular ejection fraction, however, diffuse severe hypokinesia was revealed after 3 weeks, and he died 3 months after admission because of worsening heart failure. An autopsy examination revealed eosinophilic myocarditis or hypersensitivity myocarditis with extensive fibrosis and widespread myocardial dropout throughout the heart. Learning objective: 1. Severe myocarditis occurs extremely rarely after mRNA coronavirus disease 2019 (COVID-19) vaccination. 2. Myocarditis after mRNA COVID-19 vaccination might cause complete atrioventricular block, followed by a course of decreased left ventricular ejection fraction. 3. Histologically, severe myocarditis after mRNA COVID-19 vaccination seems to present as fulminant necrotizing eosinophilic myocarditis or hypersensitivity myocarditis.

Ultrasound-guided lung biopsy with coaxial technique: pleural contact length affects the occurrence of pneumothorax after first puncture.

PURPOSE: To assess prebiopsy characteristics influencing the occurrence of pneumothorax after first puncture of ultrasound (US)-guided lung biopsy with coaxial technique. MATERIALS AND METHODS: From January 2007 to September 2018, 180 peripheral lung lesions in 174 patients who underwent B-mode US-guided lung biopsy with coaxial technique at single institution were included in this study. Technical success was defined as the ability to make a diagnosis using the acquired sample with/without an adverse event of pneumothorax. Statistical analyses of prebiopsy characteristics were performed to identify the most important cutpoint and to evaluate the effect on diagnostic accuracy. RESULTS: Of the 180 lesions (mean size, 37 mm ± 26.2; mean pleural contact length, 38.2 mm ± 34.4), technical success rate was 97.2% (175/180 lesions) and diagnostic accuracy rate was 91.6% (165/180 lesions). Pneumothorax occurred immediately after first puncture for seven of 180 lesions. Classification and regression tree analysis and Fisher's exact test showed the proportion of the pneumothorax immediately after first puncture was higher in lesions with pleural contact length less than 9.78 mm (p = 0.002). No significant difference was shown between the pneumothorax and non-pneumothorax after first puncture in technical success and final diagnosis success rate. CONCLUSION: Pleural contact length affects the occurrence of pneumothorax after first puncture of US-guided lung biopsy with coaxial technique.

Temporal changes in magnetic resonance imaging appearance of adult granulosa cell tumor.

Granulosa cell tumors (GCTs) can have a wide variety of appearances on magnetic resonance imaging (MRI), ranging from entirely solid to multilocular cystic, suggesting that GCTs undergo remarkable morphological changes during growth. These temporal changes in MRI appearance of individual GCTs have not been documented. A 54-year-old asymptomatic postmenopausal woman was referred to our department for a small ovarian mass. This 3-cm solid mass showed high intensity on diffusion-weighted MRI and low intensity on apparent diffusion coefficient mapping. Close clinical follow-up was recommended, but she did not return to our hospital until the age of 63, when she was referred for a large ovarian tumor. MRI showed a 15-cm multilocular cyst containing a solid component with hemorrhaging. Postoperative diagnosis was adult GCT (AGCT). These temporal changes demonstrate a possible reason why GCTs can have such a wide range of MRI appearance. This knowledge might promote accurate preoperative diagnosis of AGCTs.

A case of a malignant serous neoplasm of the pancreas with synchronous vascular invasion and metachronous metastases.

Serous neoplasms (SNs) of the pancreas are usually considered benign tumors. However, they rarely manifest malignant behaviors. Here we present a case of malignant SN and review the literature of malignant SN. A 71-year-old woman presented to our hospital with a palpable abdominal mass. Imaging studies revealed a 7 cm mass with a cluster of microcysts having a honeycomb appearance in the head of the pancreas, which invaded the superior mesenteric vein (SMV). After being clinically diagnosed with SN, pancreaticoduodenectomy was performed with resection of limited SMV. Microscopically, the tumor was diagnosed as an SN concomitant with the tumor thrombus in the SMV. Four years after the surgery, two liver tumors and two peritoneal nodules were detected and three of them were surgically resected. All of those lesions had a honeycomb appearance in their cut surfaces and they were microscopically indistinguishable from the originally resected SN. A review of the literature identified 22 cases of malignant metastatic SNs published to date. Even though extremely rare, metachronous metastasis could occur in SNs of the pancreas. Local invasion indicated an increased likelihood of future metastasis. Thus, periodic surveillance should be considered for SNs after resection, especially when they have a local invasion.

Evaluation of predictors of unfavorable pathological features in men eligible for active surveillance using radical prostatectomy specimens: a multi-institutional study.

OBJECTIVE: Active surveillance has emerged as an alternative to immediate treatment in men with favorable-risk prostate cancer; however, consensus about defining the appropriate candidates is still lacking. To examine the factors predicting unfavorable pathology among active surveillance candidates, we assessed low-risk radical prostatectomy specimens. METHODS: This retrospective study included 1753 men who had undergone radical prostatectomy at six independent institutions in Japan from 2005 to 2011. Patients who met the active surveillance criteria were categorized depending on the pathological features of the radical prostatectomy specimens. 'Reclassification' was defined as upstaging (≥pT3) or upgrading (radical prostatectomy Gleason score ≥7), and 'adverse pathology' was defined as pathological stage ≥pT3 or radical prostatectomy Gleason score ≥4 + 3. Multivariate analysis was used to analyze the preoperative factors for reclassification and adverse pathology. The rates of reclassification and adverse pathology were evaluated by classifying patients according to biopsy core numbers. RESULTS: The active surveillance criteria were met by 284 cases. Reclassification was identified in 154 (54.2%) cases, while adverse pathology in 60 (21.1%) cases. Prostate-specific antigen density and percentage of positive cores were independently associated with reclassification and adverse pathology. The rates of reclassification and adverse pathology were significantly higher among patients with <10 biopsy cores than among others. Thus, focusing on 149 patients with ≥10 biopsy cores, prostate-specific antigen density was the only independent predictor of unfavorable pathological features. The receiver operating characteristic curve analysis determines an optimal cut-off value of prostate-specific antigen density as 0.15 ng/ml2. CONCLUSIONS: Prostate-specific antigen density is the most important predictor of unfavorable pathological features in active surveillance candidates.

Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive Intracranial Immature Teratoma.

Immature teratoma (IMT) is the most frequent histological subtype of infantile intracranial teratoma, the most common congenital brain tumor. IMT contains incompletely differentiated components resembling fetal tissues. Infantile intracranial IMT has a dismal prognosis, because it is often inoperable due to its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to be effective in decreasing tumor volume and vascularity to facilitate surgical resection in other types of infantile brain tumors. However, only one recent case report described the effectiveness of neoadjuvant chemotherapy for infantile intracranial IMT in the literature, even though it is common entity with a poor prognosis in infants. Here, we describe the case of a 2-month-old male infant with a very large intracranial IMT. Maximal surgical resection was first attempted but was unsuccessful because of severe intraoperative hemorrhage. Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered with the aim of shrinking and devascularizing the tumor. After neoadjuvant chemotherapy, tumor size did not decrease, but intraoperative blood loss significantly decreased and near-total resection was achieved by the second and third surgery. The patient underwent adjuvant CARE chemotherapy and has been alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant chemotherapy does not decrease tumor volume of infantile intracranial IMT, surgical resection should be tried because chemotherapy can facilitate surgical resection and improve clinical outcome by reducing tumor vascularity.

Immunoglobulin G4-related disease presenting as bilateral ovarian masses and mimicking advanced ovarian cancer.

Immunoglobulin G4-related disease (IgG4-RD) is characterized by extensive infiltration of IgG4(+) plasma cells and fibrosis in various organs. However, the involvement of the ovary in IgG4-RD has never been reported. A 59-year-old woman presented with urinary retention. Magnetic resonance imaging and computed tomography revealed a huge multinodular pelvic mass and common iliac/para-aortic lymph node swelling. A laparotomy was performed under the suspicion of advanced ovarian cancer, and the pelvic mass was identified as ovary in origin. Histopathology of the excised tumor revealed massive lymphoplasmacytic infiltration (>90% were IgG4(+) plasma cells), storiform fibrosis, and obliterative phlebitis; thus leading to a diagnosis of IgG4-RD. We conclude that IgG4-RD can present as a bilateral ovarian mass along with lymphadenopathy, therefore mimicking ovarian cancer.

Successful treatment of two consecutive cases of pulmonary pleomorphic carcinoma with platinum chemotherapy.

Pulmonary pleomorphic carcinoma (PPC) is a rare pulmonary malignant tumor that has a more aggressive clinical course and a poorer prognosis compared with non-small cell lung cancer (NSCLC) due to its resistance to chemotherapy and radiotherapy. In patients with advanced or relapsed PPC, it has been reported that the response rate to chemotherapy regimens known to be effective in patients with NSCLC is only 0-17%. The present study reports the cases of two consecutive patients with advanced PPC who exhibited marked responses to chemotherapy with carboplatin plus paclitaxel chemotherapy and long-term survival without tumor progression. This suggests that carboplatin plus paclitaxel chemotherapy is a good option for the treatment of advanced PPC.

[A case of leptomeningeal melanomatosis presenting with right abducens nerve palsy].

A 39 year-old man was admitted to this hospital because of severe headache and vomiting. He had been suffering from lumbago about one month previously, and diplopia ten days previously. The neurological examination revealed disturbance of right eye abduction, no nuchal rigidity. The cerebrospinal fluid (CSF) at the time of admission included erythrocytes (1,490/µl), white blood cell (62/µl) and increased level of protein (531 mg/dl), but no malignant cells were detected. He was treated as meningitis. Cranial magnetic resonance imaging (MRI) demonstrated heterogeneous intensity lesion in the left maxillary sinus and gadolinium enhancement of diffuse meninges and cranial nerves. Spine MRI showed gadolinium enhancement of lumbar spinal meninges and the cauda equina. Biopsy of the lesion in the left maxillary sinus was performed. The pathological findings demonstrated malignant melanoma. Because malignant cells were also observed in CSF, we diagnosed this case as leptomeningeal melanomatosis. Leptomeningeal carcinomatosis should be suspected when headache accompanied with pleomorphic clinical manifestations.

[Multiple lung metastases from cutaneous adenoid cystic carcinoma resected 21 years before].

A 79-year-old woman whose cutaneous tumor had been resected 21 years and 12 years (local recurrence)before pathologically confirmed as primary cutaneous adenoid cystic carcinoma (ACC), was referred to our hospital for the abnormal shadow on chest X-ray. Chest computed tomography (CT)revealed 3 nodules in the peripheral field of both lungs, which were diagnosed by echo-guided needle biopsy as metastasis from the cutaneous ACC, and were completely resected at 5 months intervals. Any recurrences have not been detected for 2 years after the lung resection. In primary cutaneous ACC, not only complete resection with adequate margin but long-term follow up is recommended.

[Percutaneous renal mass biopsy after indeterminate diagnostic imaging results].

We conducted a retrospective study to examine the efficacy of renal mass biopsies in our hospital. Twenty-six patients (18 male, 8 female ; median age, 69 years ; range, 42-85 years) with renal masses were divided into two groups. Group 1 (n＝9) underwent renal mass biopsies after completion of diagnostic imaging tests that needed a pathological diagnosis before treatment other than extirpative surgery, and group 2 (n＝17) underwent renal mass biopsies after completion of indeterminate diagnostic imaging tests that did not rule out malignancy. The median tumor size was 2.8cm (range, 0.8-15 cm), and the median number of biopsy cores obtained was two (range, 2-4). There were no biopsy-associated complications that required intervention. In group 1, 100% (9 of 9) of the renal mass biopsies were diagnostic, and the pathological findings corresponded to the respective diagnosis obtained by imaging tests, most of which were clear cell carcinoma. In group 2, 59% (10 of 17) of the biopsies were diagnostic. The imaging characteristics of the seven nondiagnostic biopsies in group 2 were low blood flow and poor peripheral clarity. On the other hand, renal mass biopsies were indispensable for some patients in group 2 in whom the pathological findings led to a decision of treatment strategy. In conclusion, renal mass biopsies should be considered in view of their ability to compensate for limitations of imaging tests and their low frequency of complications.

A novel surgical approach to refractory hepatic hydrothorax.

Hepatic hydrothorax is defined as the presence of a pleural effusion in a patient with liver cirrhosis in the absence of cardiopulmonary disease, and it is a devastating complication impairing quality of life in the end stage of liver disease. The management of the effusion is challenging, and chest tube drainage can sometimes cause more serious complications by removing massive amounts of protein-rich fluid. Though the most plausible mechanism is the influx of ascites to the pleural cavity through a small diaphragmatic defect, the defect often cannot be found. Hepatic hydrothorax could be controlled by repairing an invisible defect of the diaphragm. With pneumoperitoneum after intraperitoneal administration of indocyanine green, the defect, clearly dyed green, appeared on the diaphragm. This novel combination technique could be useful for ensuring the surgical repair of an invisible diaphragmatic defect.

Immunoglobulin G4-related disease with scant tissue IgG4.

A 56-year-old man was admitted to our hospital for renal dysfunction and symmetrical swelling of submandibular glands. Laboratory and imaging findings were consistent with immunoglobulin G4-related disease (IgG4RD). Histological findings of the submandibular gland and the kidney were also consistent with IgG4RD. However, the patient did not have elevated serum or tissue IgG4 levels. Oral prednisolone therapy, initially 50 mg/day and gradually tapered over 12 months, improved his laboratory abnormalities and the swelling of his affected organs. These findings prompted our final diagnosis of IgG4RD. IgG4RD is a newly recognised disease with an unknown aetiology. This case suggests that IgG4 antibodies do not play a primary role in the aetiology of IgG4RD. Furthermore, clinicians should not exclude the diagnosis of IgG4RD in patients lacking elevated IgG4 levels in their affected tissues, particularly if they have other features of IgG4RD. Steroid therapy should be considered for such patients.

AP-VAS 2012 case report: a case of lupus nephritis with predominant synchronous cellular crescent formation and myeloperoxidase-antineutrophil cytoplasmic antibody seropositivity.

Several cases with an overlap of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) and lupus nephritis (LN) features have been reported in recent years. However, the clinical and the pathologic features of this condition, including mode of development, histology, and response to treatment, are not fully understood. We report a 77-year-old woman who was diagnosed with Sjögren syndrome 15 years previously. The patient presented with acute worsening of renal function and was diagnosed with new-onset systemic lupus erythematosus. A renal biopsy specimen revealed proliferative LN with synchronous cellular crescents. She was also seropositive for myeloperoxidase-ANCA. Together with the positive staining for immunoglobulins and complement factors on immunofluorescence microscopy and scant subendothelial deposits by electron microscopy, we reached a diagnosis of ANCA-associated crescentic GN overlapping with LN. Although immunosuppressive treatment with methylprednisolone pulse therapy and intravenous cyclophosphamide followed by oral predonisolone was initiated, along with intermittent hemodialysis, these treatments did not induce remission of her GN. Therefore, she continued regular intermittent hemodialysis. However, she died because of candida pneumonia 4 months after admission. Generally, the glomeruli of patients with ANCA-associated GN exhibit different stages of crescents, namely cellular, fibrocellular, or fibrous. The histologically synchronous crescents in this case indicate that ANCA-associated GN overlapping with LN can progress more rapidly than that without LN. This overlapping type of GN may be resistant to conventional immunosuppressive therapies.

AP-VAS 2012 case report: a case of ANCA-negative crescentic glomerulonephritis complicating multiple opportunistic infections in the digestive tract.

Crescentic glomerulonephritis (GN) is one of the common causes of rapidly progressive glomerulonephritis (RPGN). Pauci-immune crescentic GN is usually associated with anti-neutrophil cytoplasmic antibody (ANCA). However, patients with pauci-immune crescentic GN who lack ANCAs have recently been reported. Approximately 10-30 % of patients with pauci-immune crescentic GN lack ANCAs. The clinical characteristics of patients with ANCA-negative pauci-immune crescentic GN are not entirely the same as patients with ANCA-positive GN, and this suggests that ANCA-negative and ANCA-positive pauci-immune crescentic GN might be different disease entities. We report a patient with ANCA-negative crescentic GN complicated with multiple opportunistic infections (Candida albicans, herpes simplex virus, and Cytomegalovirus) in the digestive tract during the course of immunosuppressive therapy. After antifungal and antiviral therapies including itraconazole, valaciclovir, and ganciclovir, she recovered from multiple opportunistic infections. The occurrence of comorbid opportunistic infections during the course of immunosuppressive therapy may not be rare in the elderly. However, a case of multiple opportunistic infections limited to the digestive tract is very rare.

Double-hit lymphoma with a feature of follicular lymphoma concurrent with clonally related B lymphoblastic leukemia : a preference of transformation for the bone marrow.

We describe a 65-year-old woman with follicular lymphoma (FL), grade 1, stage IV, which occurred concurrently with B lymphoblastic leukemia/lymphoma. Through the evaluation of FL, the cells that were morphologically suspected of having undergone transformation were found in the bone marrow, and flow cytometric and cytogenetic analyses detected the transformed population that suggested concomitant t(8;22) with typical t(14;18) FL cells. Repeated analyses of the lymph nodes demonstrated the typical morphological, phenotypic, and cytogenetic features of FL. The patient received several multiagent chemotherapy regimens, but the disease gradually became resistant, and the patient died of leukemic progression. In B-cell malignancies, cases involving both BCL2 and MYC translocations simultaneously, so-called "double-hit leukemia/lymphoma (DHL)", have occasionally been reported. Patients with this type of translocation have a very poor clinical outcome, and no standard therapy has been established. In our case, FL was supposed to have transformed into B lymphoblastic leukemia via Burkitt's lymphoma-like phase. Our case is unique in that the transformed DHL cells, derived from clonally related FL cells, showed ongoing transformation from Burkitt-like feature to B lymphoblastic leukemia exclusively in the bone marrow, which suggests that the bone marrow may provide a preferable milieu for malignant transformation. Similar cases should be accumulated and analyzed carefully.

[A case of endocrine carcinoma of the cecum treated with CDDP/VP-16].

A 41-year-old man was admitted to our hospital because of multiple liver tumors. Colonoscopy showed a mass lesion in the cecum. He was given a diagnosis of endocrine cell carcinoma by immunostaining technique, and received chemotherapy of CAPOX regimen for 3 courses. After that, he underwent second-line chemotherapy of EP(CDDP/VP-16)regimen due to deterioration of his performance status(PS), and his tumor marker NSE. He then showed dramatically improved PS, and improvement in the size of liver mets and NSE(4. 3mg/mL).