Predominance of T-bet-positive Th1 cells in infiltrating T-lymphocytes in most of active arteritis lesions of giant cell arteritis.

Immunological mechanisms through the activation of CD4-positive T-cells have been assumed to be involved in the pathogenesis of giant cell arteritis (GCA). Many studies employing frozen tissues of temporal artery biopsy, peripheral blood lymphocytes, and plasma of GCA patients have revealed the contribution of interferon-γ and interleukin-17 in both protein and mRNA levels. However, the analyses using formalin-fixed and paraffin-embedded (FFPE) tissue specimens, in which the correlation between histopathologic pictures and immunological circumstances would be elucidated, have been limited. Here, we performed the immunohistochemical analyses of infiltrating small lymphocytes in GCA lesions using FFPE specimens, especially of the subsets of CD4-positive T-cells by immunohistochemistry with antibodies against T-bet, GATA-3, RORγT, and Foxp3, which is the differentiation-specific transcription factor for Th1, Th2, Th17, and Treg cells, respectively. In these slides, the nuclear-positive staining is much more clearly and easily identifiable than the cytoplasmic staining for cytokines. The results indicate the predominance of T-bet-positive Th1 cells in infiltrating T-cells in most of active arteritis lesions of GCA. Furthermore, our data suggest the possible immunosuppressive microenvironment induced by T-reg cells and M2-type macrophages in the arteritis lesions throughout the course of GCA inflammation.

A case of severe oral mucosal GVHD induced by heterologous SARS-CoV-2 vaccination after cord blood transplantation.

Patients who have undergone hematopoietic cell transplantation (HCT) are at a higher risk of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection than the general population. Therefore, early vaccination is recommended for post-transplant patients. Although exacerbation of chronic graft-versus-host disease (cGVHD) after the initial vaccination has been reported, it is unknown whether severe cGVHD occurs when different RNA vaccines are combined. We treated a patient who developed severe oral mucosal cGVHD after receiving two different RNA vaccines. Visual inspection showed that the patient presented with typical mucocutaneous cGVHD, and cGVHD in this case responded well to low-dose steroids compared to common oral GVHD exacerbations. Histopathological findings revealed T cell, B cell, and conspicuous neutrophil infiltration. Multiple doses of SARS-Cov2 vaccination are required in post-transplant recipients. In conclusion, it is essential to obtain the vaccination history of allo-HSCT recipients with cGVHD exacerbation. Furthermore, reviewing the pathological findings may help treat patients with lower doses of steroids.

Intrathoracic lipoma of chest wall misdiagnosed as liposarcoma with malignant features based on radiological image and intraoperative findings.

Lipomas are common benign tumors, which are usually located in the subcutaneous tissue. It is relatively rare for lipoma to occur in the intrathoracic cavity, and it is clinically difficult to distinguish it from liposarcoma. We present the case of a 72-year-old man with a chest wall tumor preoperatively diagnosed as liposarcoma, with tumor enlargement with radiological image change to heterogenous and 18F-fluorodeoxyglucose positron emission tomography uptake. The tumor was resected along the chest wall, lung and diaphragm because of dense adhesions. The tumor was diagnosed as lipoma with fat necrosis and inflammatory changes.

Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia.

Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are distinct entities of blood neoplasms, and the exact developmental origin of both neoplasms are considered be heterogenous among patients. However, reports of concurrent LCH and AML are rare. Herein we report a novel case of concurrent LCH and AML which shared same the driver mutations, strongly suggesting a common clonal origin.An 84-year-old female presented with cervical lymphadenopathy and pruritic skin rash on the face and scalp. Laboratory tests revealed pancytopenia with 13% of blasts, elevated LDH and liver enzymes, in addition to generalised lymphadenopathy and splenomegaly by computed tomography. Bone marrow specimens showed massive infiltration of MPO-positive myeloblasts, whereas S-100 and CD1a positive atypical dendritic cell-like cells accounted for 10% of the atypical cells on bone marrow pathology, suggesting a mixture of LCH and AML. A biopsy specimen from a cervical lymph node and the skin demonstrated the accumulation of atypical cells which were positive for S-100 and CD1a. LCH was found in lymph nodes, skin and bone marrow; AML was found in peripheral blood and bone marrow (AML was predominant compared with LCH in the bone marrow). Next generation sequencing revealed four somatic driver mutations (NRAS-G13D, IDH2-R140Q, and DNMT3A-F640fs/-I715fs), equally shared by both the lymph node and bone marrow, suggesting a common clonal origin for the concurrent LCH and AML. Prednisolone and vinblastine were initially given with partial response in LCH; peripheral blood blasts also disappeared for 3 months. Salvage chemotherapy with low dose cytarabine and aclarubicin were given for relapse, with partial response in both LCH and AML. She died from pneumonia and septicemia on day 384. Our case demonstrates a common cell of origin for LCH and AML with a common genetic mutation, providing evidence to support the proposal to classify histiocytosis, including LCH, as a myeloid/myeloproliferative malignancy.

Eosinophilic Fasciitis with Hypereosinophilia as the Initial Clinical Manifestation of Peripheral T-Cell Lymphoma, Not Otherwise Specified.

A 58-year-old man presented with painful edema of the extremities, and a diagnosis of eosinophilic fasciitis (EF) was confirmed. He also met the criteria for hypereosinophilic syndrome (HES), but there were no findings suggestive of malignancies or hematologic neoplasms despite a close examination. He was started on steroid therapy but subsequently developed severe liver dysfunction, hemophagocytic lymphohistiocytosis, hepatosplenomegaly, and renal involvement. The diagnosis of peripheral T-cell lymphoma, not otherwise specified was finally established by a bone marrow reexamination and liver biopsy. In cases of eosinophilia, EF, and/or HES, it is important to suspect an intrinsic abnormality, including potential T-cell lymphoma.

Clinical Characteristics of Posttransplant Lymphoproliferative Disorder After Cord Blood Transplantation Without Antithymocyte Globulin.

BACKGROUND: CBT with ATG use is a well-known PTLD risk factor. However, little is known regarding the clinical features of PTLD after ATG-free CBT. PATIENTS AND METHODS: We analyzed the incidence, risk factors and prognosis of PTLD in 183 adults undergoing ATG-free CBT. RESULTS: Fifteen patients (diffuse large B-cell lymphoma, n = 9, mucosa-associated lymphoid tissue lymphoma, n = 2 nondestructive PTLD, n = 1, T-cell lymphoma, n = 3) developed PTLD. The 2-year CuI of PTLD was 8.0% (95% CI: 4.6-12.7). Pathologically, all 12 B-cell PTLD patients had Epstein-Barr virus (EBV), compared with 1 of 3 T-cell PTLD patients. All patients, excluding one with nondestructive PTLD, showed extranodal involvement. In the univariate analysis, the 2-year CuI of PTLD was significantly higher in patients who received mycophenolate mofetil to prevent graft-versus-host disease than in nonrecipients (11.2%/2.9%, P = .0457). However, multivariate analysis revealed no independent PTLD risk factors. All 11 PTLD patients who received specific therapy achieved complete remission. The 1-year overall survival of PTLD patients was 70.9%. CONCLUSION: Although we found a higher CuI of PTLD than previously reported, the prognosis was generally good. In CBT recipients, many factors, including MMF use, may be associated with the clinical features of PTLD.

IgG4-related Disease with a Cardiac Mass Causing Cerebral Infarction.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by infiltration of extensive IgG4-positive plasma cells and lymphocytes. Although IgG4-RD has been observed in almost all organs, it rarely affects the myocardium. Cardiovascular lesions of IgG4-RD appear as aortic (aortic aneurysm and aortitis) and pericardial (constrictive pericarditis) lesions as well as pseudotumors around the coronary arteries. We herein report a case of IgG4-RD with a cardiac mass in the right atrium involving a sinus node. This condition caused arrhythmia and repeated strokes. We successfully treated the patient through resection of the cardiac mass, catheter ablation and immunosuppressive therapy.

Rapid Improvement in Jaundice Using Transdermal Isosorbide Tape as a Nitric Oxide Donor in Two Adult Patients with Transplantation-associated Microangiopathy Related to Graft-versus-host Disease.

Two adult patients with acute leukemia developed transplantation-associated microangiopathy (TAM) related to graft-versus-host disease (GVHD). Both patients were resistant to standard therapy for TAM and GVHD, which led to markedly elevated serum total bilirubin levels of 47.5 and 10.6 mg/dL, respectively. Transdermal isosorbide tape as a nitric oxide donor was applied to Patients 1 and 2 on post-transplantation days 60 and 66, respectively, which rapidly improved their jaundice after 1 day. This is the first report to describe the efficacy of transdermal isosorbide tape for adult patients with jaundice associated with TAM related to GVHD.

Serial Cancer Development Three Times in a Patient with Fanconi Anemia.

Fanconi anemia (FA) is characterized clinically by bone marrow failure, congenital malformations, sensitivity to DNA cross-linking agents, and increased risk of malignancy. Hematological cancer is the best-described malignancy in patients with FA, but the susceptibility to the development of solid tumors is also well documented, especially after hematopoietic stem cell transplantation (HSCT). With regard to the development of solid tumors in patients with FA, head and neck, esophageal, and anal squamous cell carcinoma are well known, but reports of lung cancer are extremely rare. Here, we describe an FA patient with a history of HSCT that developed 3 serial cancers - oral, esophageal, and nonsmall cell lung cancer - over a period of 6 years. The third lesion was nonsmall cell lung cancer and its location corresponded closely to the field of irradiation treatment for prior esophageal cancer. The occurrence of lung cancer in patients with FA is uncommon, but FA patients should be screened regularly and serially. Our case also indicated the importance of the irradiated field as a location for subsequent cancer development.

Preoperative prediction of the localization of a solitary fibrous tumor using four-dimensional computed tomography: a case report.

Solitary fibrous tumors of the pleura (SFTP) are relatively rare primary pleural tumors. Four-dimensional computed tomography (4D-CT) is reportedly useful in assessing parietal pleural invasion and adhesion in patients with lung cancer. We report a case in which 4D-CT was performed to evaluate SFTP localization and parietal pleural invasion and adhesions. A 62-year-old female presented with an abnormality on a chest radiograph. Chest CT revealed a well-demarcated solid nodule in the left lower lobe adjacent to the pleura. We considered that the tumor was intrapulmonary or arose from the visceral pleura, without adhesion or invasion to the chest wall based on 4D-CT. Primary lung cancer was suspected, and the tumor was resected. Pathological diagnosis revealed an SFTP. This case suggests that 4D-CT is useful in predicting the localization of SFTP and other thoracic tumors, assessing chest wall adhesion and invasion, and making surgical strategies.

Primary posterior mediastinal angiolipoma: a case report.

An angiolipoma is a benign tumor, and a primary mediastinal angiolipoma is extremely rare. Herein, we describe the presentation and management of a posterior mediastinal angiolipoma in a woman with loss of consciousness. Chest computed tomography (CT) revealed a contrast-enhancing mass in the right posterior mediastinum, with intercostal arterial blood supply identified on three-dimensional reconstruction CT (3D-CT). Magnetic resonance imaging revealed a fatty component. Pre-operative embolization of the supplying intercostal artery was performed to reduce intraoperative bleeding. Mass resection was performed using video-assisted thoracic surgery. Histopathology confirmed angiolipoma diagnosis. Although rare, a posterior mediastinum angiolipoma should be considered a possibility; 3D-CT and pre-operative embolization may be useful in the surgical treatment of hypervascular mediastinal tumors, such as angiolipomas.

A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.

Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.

Pulmonary metastasis with coexisting pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma 20 years after endometrioid adenocarcinoma surgery: A case report.

Late pulmonary metastasis from endometrioid adenocarcinoma (EA) is rare, and occurrence after >20 years is extremely rare. Here, we report a case of pulmonary metastasis with coexisting pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma that occurred 20 years after surgery for EA. A 60-year-old Japanese woman had previously undergone surgery for primary EA, and 20 years later presented with an abnormality that was detected on chest radiography. Chest computed tomography (CT) revealed two nodules in the right lower lung lobe, which were suspected to be primary lung cancer. Wedge resection was performed, and the intraoperative pathological diagnosis was that of adenocarcinoma with MALT lymphoma; this prompted additional right lower lobectomy. The final pathological diagnosis was pulmonary metastasis from EA with coexisting MALT lymphoma. This is probably the first report on late pulmonary metastasis coexisting with MALT lymphoma 20 years after surgery for EA. Surgeons should be aware of the possibility of late pulmonary recurrence of EA after more than 20 years and should consider aggressive resection. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Although extremely rare, pulmonary metastasis can occur more than 20 years after surgery for endometrioid adenocarcinoma. Furthermore, pulmonary metastasis from endometrioid adenocarcinoma may coexist with mucosa-associated lymphoid tissue lymphoma. WHAT THIS STUDY ADDS: Endometrioid adenocarcinoma requires long-term postoperative follow-up to detect recurrence, even in early-stage cases. Video-assisted thoracoscopic surgery (VATS) is useful for resecting pulmonary metastasis from endometrioid adenocarcinoma.

Surgical resection of a middle mediastinal paraganglioma that caused diabetes.

BACKGROUND: Paragangliomas are rare neuroendocrine tumors originating from chromaffin cells of extra-adrenal origin. Ninety percent of adrenergic tumors originate in the adrenal medulla and are known as pheochromocytomas; the remaining 10% are extra-adrenal and are called paragangliomas. Mediastinum paragangliomas is rare and commonly originate from the posterior mediastinum, while those originating from the middle posterior are quite rare. Some paragangliomas secrete catecholamines, leading to symptoms such as hypertension, tachycardia, and diabetes. CASE PRESENTATION: A 76-year-old woman visited our hospital for the treatment and further evaluation of diabetes. Her hemoglobin A1c levels had risen to 11.0%. To investigate the cause of her diabetes, a contrast-enhanced chest computed tomography scan was performed, revealing a ring-enhancing tumor (30 × 30 mm) in the middle mediastinum. The surgical resection was performed via video-assisted thoracic surgery. Surgery was performed using a vessel-sealing device; however, bleeding was persistent from the surrounding tissue. Total bleeding was 400 g. Blood pressure fluctuations and arrhythmia did not occur during the operation. The patient's uncontrolled diabetes was cured after the surgery, and the tumor was diagnosed as a functional paraganglioma. CONCLUSIONS: We encountered a rare case of functional paraganglioma located in the middle mediastinum. Functional paragangliomas should be considered as a potential cause of uncontrolled diabetes, and a whole-body CT scan should be performed to investigate this possible cause.

The ratio of CD163-positive macrophages to Iba1-positive macrophages is low in the intima in the early stage of cutaneous arteritis.

The etiology of polyarteritis nodosa (PAN) and localized PAN, including cutaneous arteritis (CA), remains unknown; however, initial endothelial damage has been implicated. The intima of the vasculitis lesions is predominantly infiltrated by innate-like bystander-activated CD8 T cells, in addition to the macrophages. Macrophages are among the major inflammatory cells involved in innate immunity and are classified into M1 and M2 subtypes. M1-type macrophages kill pathogens and cause inflammation, while M2-type macrophages promote the repair of tissues. Macrophage subtypes infiltrating in PAN and localized PAN vasculitis lesions have not yet been investigated. Innate immune response to a triggering factor on the endothelial cell surface may initiate CA pathogenesis. Thus, many M1-type macrophages may infiltrate in the intima during early CA. We assessed this hypothesis by immunohistochemical observation of macrophage phenotypes and polarization. Twenty-seven skin biopsy specimens from patients with CA were retrieved. Based on histology, we classified CA into four phases. The phenotypes of infiltrating macrophages in CA were evaluated by immunohistochemistry using antibodies against Iba-1, a pan-macrophage marker, and CD163, an M2-type macrophage marker. Our results showed that the ratio of CD163-positive M2-type macrophages to Iba1-positive macrophages was lower in the intima in the early stage of CA than in the later stage. In the media to adventitia, there was no significant difference in the ratios between these stages. These findings indicate that innate immunity is involved in the intima in the early stage of CA, suggesting that a trigger for CA might exist in endothelial cells.

Type B3 thymoma with marked neuroendocrine differentiation: Report of a case.

Thymomas are tumors originating from the thymus epithelial cells and are the most common tumors of the anterior mediastinum. They have been classified into types A, AB, B1, B2, and B3 by the World Health Organization. Type B3 thymoma is composed of epithelial cell sheets with mild to moderate atypia and scant lymphocytes. An association between thymic carcinoma and neuroendocrine differentiation has been observed by some authors. However, cases of type B3 thymoma with neuroendocrine differentiation are very rarely discussed in the literature. A 68-year-old woman was referred to our hospital with an abnormal shadow on a chest roentgenogram. Chest computed tomography showed that the lesion was located in the anterior mediastinum. She underwent surgery, and the tumor was diagnosed as a type B3 thymoma with neuroendocrine differentiation. An extremely rare case of a type B3 thymoma showing neuroendocrine differentiation is presented herein.

Eosinophilic granulomatosis with polyangiitis complicated by subarachnoid hemorrhage and coronary vasculitis: a case report and review of the literature.

Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by necrotizing vasculitis of small-sized vessels with extravascular granulomas and eosinophilic infiltration. The case of a 48-year-old Japanese woman with EGPA, who presented concurrently with subarachnoid hemorrhage (SAH) and coronary vasculitis, is reported. She initially presented with bronchial asthma, and then 8 months later she developed various symptoms caused by systemic eosinophilic vasculitis and was admitted to our hospital. Three days after admission, she started oral corticosteroid therapy, and her 2009 Five-Factor Score (FFS) was 0. However, she developed an SAH, followed by coronary vasculitis 1 day later. With extensive treatment with a combination of betamethasone, cyclophosphamide, intravenous immunoglobulin, and rituximab, her systemic vasculitis improved dramatically. This seems to be the first case of EGPA with SAH and coronary vasculitis. In previous reports of EGPA with SAH, 4 of 11 cases developed SAH as an exacerbation of systemic vasculitis during remission induction therapy. The present patient also had SAH during remission induction therapy. However, the period between bronchial asthma and SAH was only 8 months. This is the shortest among case reports of EGPA with SAH. In addition, the present patient rapidly developed coronary vasculitis. These findings suggest that EGPA causes SAH and coronary vasculitis as early complications of systemic vasculitis. In EGPA, it is necessary to pay careful attention to rapid changes of disease activity, even when the FFS indicates a good prognosis.

Extramedullary Plasmacytoma Arising From the Anterior Mediastinum.

Plasmacytomas are a localized proliferation of plasma cells in the bone marrow and soft tissue. Extramedullary plasmacytomas are rare and typically solitary plasma cell neoplasms originating from extraosseous organs and tissues. A 31-year-old woman was referred to our hospital with a rapidly growing abnormal shadow on a chest roentgenogram. Chest computed tomography showed that the lesion was located in the anterior mediastinum. She underwent surgery, and the tumor was diagnosed as an extramedullary plasmacytoma. She remains well 2 years postoperatively without recurrence. An extremely rare case of an anterior mediastinal extramedullary plasmacytoma is presented.

Fatal cardiac anomaly of unguarded mitral orifice with asplenia syndrome.

We report the case of a newborn baby with an unguarded mitral orifice associated with asplenia syndrome, double-outlet right ventricle, dysplastic tricuspid valve, and pulmonary stenosis. This case was accompanied by severe tricuspid regurgitation and severe right ventricular hypertrophy. The patient had a fatal clinical course due to severe hypoxia and congestive heart failure. Unguarded mitral orifice is a rare disease in which there has been no previous report of lethal clinical course during the neonatal period. Prior reports stated that unguarded mitral orifice was a new constellation of defects and that its etiology and embryology could be classified in the same category because of similar associated malformations of double-outlet right ventricle and pulmonary stenosis or atresia. However, the present case was diagnosed on autopsy as also having asplenia syndrome. Therefore, it is possible that the genetic etiology of unguarded mitral orifice in this case was different from cases of non-heterotaxy. .