Wide local extension and higher proliferation indices are characteristic features of symptomatic lobular neoplasias (LNs) and LNs with an early invasive component.

AIMS: Lobular neoplasias (LNs) are typically small, clinically undetectable breast lesions, but some LNs are of clinical significance. The aim of this study was to clarify the histopathological characteristics of clinically overt (symptomatic) LNs and early invasive LNs. METHODS AND RESULTS: Sixty-two surgically resected LNs, including eight with early invasion (≤10 mm), were classified into the following groups: (i) symptomatic and occult; and (ii) early invasive and non-invasive. Six histopathological factors, including the Ki67 labelling index (LI), were assessed and analysed by logistic regression models. On multivariate analysis, tumour size (P = 0.008), mitotic counts (P = 0.006) and Ki67 LI (P = 0.035) were risk factors for symptomatic features, and tumour size (P = 0.009) and Ki67 LI (P = 0.015) were risk factors for early invasive lesions. In the eight LNs with invasion, the symptomatic and occult subgroups showed differing nuclear atypia and structural patterns, but both lesions extended widely (22-96 mm). CONCLUSIONS: Wide extension and higher proliferation activity were characteristic features of symptomatic LNs and LNs with early invasion.

Transition from endocapillary proliferative glomerulonephritis to membranoproliferative glomerulonephritis in a patient with a prolonged human parvovirus B19 infection.

We report a case in which renal biopsies were performed 4 years apart in a woman with a prolonged human parvovirus B19 (HPB19) infection. When she was 29 years old the first biopsy, performed because of microscopic hematuria and mild proteinuria, showed endocapillary and mesangial proliferative glomerulonephritis in light microscopy as well as deposits of immunoglobulins (Igs) and complement C3 on capillary walls. Mesangial, intramembranous, and subepithelial hump-like electron dense deposits were seen in electron microscopy. The principal differential diagnoses, acute poststreptococcal glomerulonephritis and lupus nephritis, were unlikely, and her serological positivity for IgM antibody for HPB19 made us diagnose acute glomerulonephritis associated with HPB19 infection. The second biopsy, performed 4 years later because of persistent proteinuria and prolonged positivity for IgM antibody for HPB19, showed membranoproliferative glomerulonephritis (MPGN) with mesangial interposition and with thickening and double contours of glomerular basement membrane. In tissues obtained in both biopsies, HPB19 DNA was detected by polymerase chain reaction. HPB19 infection has been widely known to cause various glomerular diseases. This case reveals that acute endocapillary proliferative glomerulonephritis can change into MPGN during prolonged HPB19 infection.

Community-acquired lobar pneumonia caused by Pseudomonas aeruginosa infection in Japan: a case report with histological and immunohistochemical examination.

Pseudomonas aeruginosa is a common pathogen in nosocomial and/or healthcare-associated pneumonia, but is rare in community-acquired pneumonia. A 50-year-old previously healthy woman was taken to the emergency department because of rapidly progressing dyspnea. Chest radiograph showed consolidation of the entire right upper lobe, a finding suggestive of lobar pneumonia. The patient died of respiratory failure with bronchial bleeding, on the same day of admission. Autopsy revealed that the alveoli throughout the upper right lobe were filled with dense inflammatory cells mainly consisting of macrophages and neutrophils. Immunoreactive bacilli by using an anti-P. aeruginosa antibody were localized within macrophages accumulated in the alveoli as well in the vessel walls. Lobar pneumonia composed of dense neutrophils and bacteria-laden macrophages with total lung congestion and edema may be characteristic for community-acquired P. aeruginosa pneumonia in a healthy adult.

Mucinous breast carcinoma with a lobular neoplasia component: a subset with aberrant expression of cell adhesion and polarity molecules and lack of neuroendocrine differentiation.

We investigated whether some mucinous carcinomas (MUCs) are associated with lobular neoplasia (LN) components, and if so, whether this subset has any distinct biological properties. MUC specimens from 41 patients were stratified into pure and mixed types. The LN components adjacent to MUC lesions were examined histopathologically. We also tested immunohistochemically for E-cadherin, ß-catenin, and the neuroendocrine markers chromogranin A and synaptophysin; and compared results between MUCs with and without LN. Of 41 patients with MUC, LN was detected in 12 patients (29%); LN alone was the noninvasive component in 8 patients (20%). Decreased E-cadherin and ß-catenin expression in the MUC component was detected in 2 (17%) and 7 (58%) cases, respectively, of MUC with LN, compared with 0% (P = 0.080) and 21% (P = 0.018) in MUCs without LN. Neuroendocrine factors were frequently detected in MUCs with LN (42%) and without LN (52%), but tended to be less frequent in MUCs with only LN components (25%) than in other MUCs (55%; P = 0.133). MUCs associated with LN components appear to be a biologically characteristic subset that frequently shows decreased cell-cell adhesion, cell polarity molecules and lack of neuroendocrine differentiation.

IgG4-related retroperitoneal fibrosis induced by nivolumab and ipilimumab in a patient with non-small cell lung cancer: A case report.

IgG4-related diseases are adverse events that occur after receiving treatment with immune checkpoint inhibitors (ICI). This study reports the first case of IgG4-related retroperitoneal fibrosis after the administration of chemotherapy with nivolumab and ipilimumab (NI therapy). An 80-year-old man developed lower abdominal pain eight months after NI therapy was initiated. Although the primary lesion maintained its reduced size on computed tomography, there was an increase in the soft tissue shadows intensity around the abdominal aorta, bladder, and seminal vesicles, suggesting retroperitoneal fibrosis. Blood tests showed elevated IgG4 levels. Computed tomography-guided biopsy of the retroperitoneum showed B cell-dominant lymphocyte infiltration consistent with IgG4-related retroperitoneal fibrosis and characteristic CD8-positive lymphocyte infiltration, suggestive of the involvement of cytotoxic T cells. Based on the clinical, imaging, and pathological findings, the patient was diagnosed with IgG4-related retroperitoneal fibrosis due to ICI. Immunotherapy discontinuation alone did not result in improvement; therefore, steroid therapy was initiated. In clinical practice, IgG4-related retroperitoneal fibrosis can occur as an immune-related adverse event when administering anti-PD-1 and anti-CTLA-4 antibodies for cancer immunotherapy. Early steroid therapy could be effective in controlling this immune-related adverse event.

Two Cases of Acquired High-Density Lipoprotein Deficiency with Immunoglobulin G4-Related Lecithin-Cholesterol Acyltransferase Autoantibody.

Lecithin-cholesterol acyltransferase (LCAT) plays a significant role in the progression from premature to mature high-density lipoprotein (HDL) in circulation. Consequently, primary or secondary LCAT deletion or reduction naturally results in low serum HDL cholesterol levels. Recently, rare cases of acquired HDL deficiency with LCAT autoantibodies have been reported, mainly from Japan, where LCAT autoantibodies of immunoglobulin G (IgG) caused the HDL deficiency. Here to our knowledge, we report for the first time two cases of acquired HDL deficiency caused by IgG4 linked LCAT autoantibodies with or without a high serum IgG4 level. Furthermore, these cases can extend to a new concept of "IgG4 autoimmune disease" from the viewpoint of verifying the serum autoantibody and/or renal histopathology.

Acute pancreatitis coincided with multiple arteriolar aneurysms in a patient with polyarteritis nodosa.

A 78-year-old man presented to our hospital with a history of 10 kg weight loss within 6 months previously and general fatigue and fever for 2 and 1 months, respectively. On hospitalisation, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved remission with the administration of 1000 mg methylprednisolone for 3 days, followed by prednisolone (55 mg/day). Steroids were successfully tapered with no re-elevation in inflammation. Two months after the administration of steroids, the patient complained of acute abdominal pain and developed severe acute pancreatitis. During treatment for pancreatitis, the patient died due to septic shock and disseminated intravascular coagulation. An autopsy revealed necrotising vasculitis in the intrapancreatic arteries and ischaemia of the downstream arterioles resulting in acute pancreatitis.

Pleural dedifferentiated liposarcoma: A case report.

The present case report describes a rare case of pleural liposarcoma. A 45-year-old Japanese man was hospitalized for increasing left chest pain. Imaging revealed a 10-cm pleural tumor and a 1.7-cm contralateral right pulmonary nodule. Biopsy specimens of the pleural tumor showed undifferentiated spindle-shaped and/or rounded sarcomatous features with myxoid stroma. The patient underwent embolization of the arteries feeding the left pleural tumor and palliative partial resection of the pleural tumor. The surgically removed specimens exhibited similar undifferentiated sarcomatous features. The left pleural tumor regrew aggressively, and the patient succumbed to mortality ~4.2 months following hospitalization. Autopsy demonstrated a 35-cm left pleural tumor, metastasizing to both adrenal glands and lumbar vertebral bones, and a 2.2-cm primary adenocarcinoma of the right lung. The majority of the left pleural tumor and its metastases consisted of undifferentiated sarcomatous elements, however, scattered or aggregated lipoblasts were identified in localized areas adjacent to the diaphragm. Immunohistochemically, these lipoblasts were diffusely positive for MDM2 and focally positive for S-100 protein. Undifferentiated sarcomatous tumor cells were focally positive for MDM2 but negative for S-100 protein. This case was diagnosed as pleural dedifferentiated liposarcoma. The local aggressiveness of the pleural liposarcoma directly contributed to the patient's mortality. A review of the literature indicated that the dedifferentiated subtype may serve as a factor that is indicative of a poor prognosis for pleural liposarcoma.

Fulminant pseudomembranous enterocolitis caused by Klebsiella oxytoca: an autopsy case report.

CASE: We describe a rare case of antibiotic-associated fulminant pseudomembranous enterocolitis caused by Klebsiella oxytoca. A 79-year-old man with a history of antibiotic therapy was admitted to our emergency department, complaining of consciousness disturbance. Initially, we suspected septic shock and diabetic ketoacidosis caused by intestinal infection. Although we administered sufficient extracellular fluid, his blood pressure was not elevated and his abdomen gradually swelled. OUTCOME: The patient died of shock and abdominal compartment syndrome. Autopsy revealed widespread jejunal necrosis in conjunction with colitis, suggesting fulminant pseudomembranous enterocolitis caused by K. oxytoca infection. CONCLUSION: As the clinical features of pseudomembranous enterocolitis caused by K. oxytoca resemble the features of colitis caused by Clostridium difficile, conservative therapy is applied first. However, fulminant pseudomembranous enterocolitis is a lethal disease, necessitating early operation for resection of the necrotic lesion. This report highlights the need for better surgical criteria at an early stage.

Successful Corticosteroid Treatment for Purpura Fulminans Associated with Quinolone.

Purpura fulminans (PF) is a life-threatening syndrome comprising progressive hemorrhagic necrosis due to disseminated intravascular coagulation and dermal vascular thrombosis that leads to purpura and tissue necrosis. Various therapies have been used to arrest the progression of this disease, however, there is no established treatment because of the variety of underlying causes. We herein present an adult case of PF associated with leukocytoclastic vasculitis triggered by antibiotic (levofloxacin) intake. As a result of our rapid and accurate identification of the underlying cause, corticosteroid therapy successfully repressed the inflammatory process. As far as we know, this is the first report of levofloxacin-associated PF.

Mixed epithelial and stromal tumor of the kidney with polypoid component extending into renal pelvis and ureter.

Mixed epithelial and stromal tumor (MEST) of the kidney is an unusual benign neoplasm that predominantly occurs in middle-aged females. It typically appears as a well-circumscribed multiseptate mass with solid components on computed tomography (CT) or magnetic resonance image (MRI), reflecting its characteristics of an admixture of stromal proliferation and epithelial cells consisting of multiple cysts. We present a rare case of 61-year-old woman with MEST, which manifested as a multilocular cystic mass with a polypoid component protruding into the renal pelvis and ureter. To our best knowledge, this is the first case of MEST extending into the ureter.

Idiopathic nodular glomerulosclerosis in a never-smoking, normotensive, non-obese, normal-glucose-tolerant middle-aged woman.

A 53-year-old woman with a history of dyslipidemia presented with medium-grade proteinuria and several years of progressive renal dysfunction. Renal biopsy showed diffuse and global Kimmelstiel-Wilson nodule like nodular mesangial sclerosis, but she had no history of diabetes mellitus, no diabetic retinopathy and normal oral glucose tolerance. Congo red staining was negative, and immunofluorescence staining showed no immunoglobulin deposition including kappa or lambda light chains. Electron microscopy showed no electron dense deposits or organized deposits. Thus, we diagnosed idiopathic nodular glomerulosclerosis (ING). ING is a recently established clinicopathologic disease entity linked to longstanding cigarette smoking and hypertension. Obesity is also listed as a contributing factor. However, none of these factors was documented in this case. This is a valuable case of ING that suggests the existence of as-yet unknown causative factors of ING other than smoking, hypertention or obesity.

New criteria for histologic grading of colorectal cancer.

Conventional tumor grading systems based on the degree of tumor differentiation may not always be optimal because of difficulty in objective assessment and insufficient prognostic value for decision making in colorectal cancer (CRC) treatment. This study aimed to determine the importance of assessing the number of poorly differentiated clusters as the primary criterion for histologic grading of CRC. Five hundred consecutive patients with curatively resected stage II and III CRCs (2000 to 2005) were pathologically reviewed. Cancer clusters of ≥5 cancer cells and lacking a gland-like structure were counted under a ×20 objective lens in a field containing the highest number of clusters. Tumors with <5, 5 to 9, and ≥10 clusters were classified as grade (G)1, G2, and G3, respectively (n=156, 198, and 146 tumors, respectively). Five-year disease-free survival rates were 96%, 85%, and 59% for G1, G2, and G3, respectively (P<0.0001). Poorly differentiated clusters affected survival outcome independent of T and N stages and could help in more effective stratification of patients by survival outcome compared with tumor staging (Akaike information criterion, 1086.7 vs. 1117.0; Harrell concordance index, 0.73 vs. 0.67). The poorly differentiated cluster-based grading system showed a higher weighted κ coefficient for interobserver variability (5 observers) compared with conventional grading systems (mean, 0.66 vs. 0.52; range, 0.55 to 0.73 vs. 0.39 to 0.68). Our novel histologic grading system is expected to be less subjective and more informative for prognostic prediction compared with conventional tumor grading systems and TNM staging. It could be valuable in determining individualized postoperative CRC treatment.