An autopsy case of acute fibrinous and organizing pneumonia with periorbital MRSA cellulitis and rheumatoid arthritis.

This case report details a 78-year-old male with periorbital Methicillin-resistant Staphylococcus aureus (MRSA) cellulitis whose condition rapidly deteriorated despite treatment. An autopsy confirmed acute fibrinous and organizing pneumonia (AFOP), revealing fibrin ball formation and organizing pneumonia. While both idiopathic and secondary AFOP cases often exhibit bilateral consolidation on CT, our patient presented with ground-glass opacities, which are frequently associated with secondary AFOP. Notably, secondary AFOP, linked to higher mortality, can result from various factors. In this case, well-controlled rheumatoid arthritis and prolonged oral medication use suggest bilateral periorbital MRSA cellulitis as a significant factor. The study underscores AFOP's diagnostic challenges and the necessity for further research on effective treatments.

Rupture of thymoma due to recurrent tumor hemorrhage: a case report.

Background: Rupture of a thymoma is rare, and due to its rarity, the mechanism of rupture remains unclear. Here we report a case of a ruptured thymoma that ruptured due to an increase in the intratumoral pressure caused by recurrent hemorrhaging. Case Description: A 70-year-old woman presented 2 days prior persistent right chest and shoulder pain. A chest computed tomography (CT) scan revealed the presence of a mass occupying the anterior mediastinum and a right pleural effusion. It was diagnosed as an anterior mediastinum tumor. The increase in the levels of inflammatory markers and tumor necrosis observed on CT were suggestive of infection. As the general status of the patient was stable and she initially received antibiotic medical therapy, an improvement in the inflammatory marker levels was observed with antibiotic therapy. A surgical resection was performed 10 days after admission. Median sternotomy revealed a tumor extending from the mediastinum to the right thoracic cavity. Since the adhesion was strong and tumor invasion was suspected, the tumor was completely resected by combining a partial resection of the right middle and lower lobes with the pericardium. Pathological examination revealed that the tumor was a type B2 thymoma with fibrosis, necrosis, hemosiderosis, and hemorrhaging, suggesting recurrent hemorrhaging within the tumor. Conclusions: Based on the findings of our case, recurrent hemorrhaging within the tumor led to an increase in the intratumoral pressure and chronic inflammation and necrosis weakened the tumor wall. These changes contributed to the subsequent rupture.

Solitary Cardiac Metastasis from Colorectal Cancer: A Case Report.

A 73-year-old woman with silent cardiac metastasis underwent high anterior resection for rectal cancer 3 years ago. Follow-up computed tomography showed a tumor in the right atrium. Partial vascular resection of the superior vena cava and right atrium was performed. Early postoperative recurrence occurred, and chemotherapy was unsuccessful. The patient died 7 months after surgery.

A case of synchronous multiple primary lung adenocarcinomas harboring epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement successfully treated with combination of osimertinib and alectinib.

Synchronous multiple primary lung cancers (SMPLC) should be distinguished from intrapulmonary metastasis to define the optimal treatment approach. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are typically mutually exclusive and the co-existence of both mutations is relatively rare. Herein, we report a case of SMPLC harboring each EGFR mutation and ALK rearrangement successfully treated with combination of osimertinib and alectinib. A combination of EGFR- and ALK-tyrosine kinase inhibitors could be an effective and tolerable therapeutic option for SMPLC with EGFR mutations and ALK rearrangement.

On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity.

Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine γ-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au-S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm-1; patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm-1, manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance.

A case of diffuse large B-cell lymphoma originating from chest wall complicated by benign asbestos pleural effusion.

A 78-year-old man with exposure to asbestos was admitted to our hospital for back pain. A chest computed tomography showed right pleural effusion and a significant increase in the size of masses in the right chest wall over an interval of six months. He did not undergo further examinations and expired one month later. Autopsy revealed the presence of diffuse large B-cell lymphoma (DLBCL) and complicated by benign asbestos pleural effusion. We considered that this tumour had originated from the soft tissue in the chest wall based on the radiological and autopsy findings. The present report highlights that primary DLBCL of chest wall might be associated with chronic inflammation due to asbestos-related pleural diseases.

Hyperprogressive disease after treatment with pembrolizumab in lung adenocarcinoma: An autopsy case study.

Although immune-checkpoint inhibitors (ICIs) have become an important choice of treatment for advanced NSCLC, recent reports show hyperprogressive disease (HPD) after ICI administration. The clinico-pathological features of HPD still remain unclear. Here we report a 65-year-old man with lung adenocarcinoma who abruptly presented HPD two days after pembrolizumab administration. The primary tumor increased in size from 40 mm to 57 mm on the chest HRCT. The patient died on day 37 after pembrolizumab administration. The autopsy demonstrated widespread progression of cancer cells into the alveolar spaces and lymphangitic carcinomatosis in the left lung, with plenty of bloody pleural effusion. We compared the pathohistology and immunohistochemical expression of PD-L1 between the pretreatment biopsy material and posttreatment autopsy materials, and found a change in PD-L1 expression which may be related to HPD. We also discuss the possibility of HPD, pseudoprogression, and interstitial lung disease when there is evidence of tumor growth or ground glass shadows on chest images after ICI treatment.

Array comparative genomic hybridization analysis discloses chromosome copy number alterations as indicators of patient outcome in lymph node-negative breast cancer.

BACKGROUND: Patients with lymph node metastasis-negative (pN0) invasive breast cancer have favorable outcomes following initial treatment. However, false negatives which occur during routine histologic examination of lymph nodes are reported to underestimate the clinical stage of disease. To identify a high-risk group in pN0 invasive breast cancer, we examined copy number alterations (CNAs) of 800 cancer-related genes. METHODS: Using array-based comparative genomic hybridization (CGH) in 51 pN0 cases (19 relapsed and 32 non-relapsed cases), the positivities of specific gene CNAs in the relapsed and non-relapsed groups were compared. An unsupervised hierarchical cluster analysis was then performed to identify case groups that were correlated with patient outcomes. RESULTS: The cluster analysis identified three distinct clusters of cases: groups 1, 2, and 3. The major component was triple-negative cases (69%, 9 of 13) in group 1, luminal B-like (57%, 13 of 23) and HER2-overexpressing (26%, 6 of 23) subtypes in group 2, and luminal A-like subtype (60%, 9 of 15) in group 3. Among all 51 cases, those in group 1 showed significantly worse overall survival (OS) than group 2 (p = 0.014), and 5q15 loss was correlated with worse OS (p = 0.017). Among 19 relapsed cases, both OS and relapse-free survival (RFS) rates were significantly lower in group 1 than in group 2 (p = 0.0083 and 0.0018, respectively), and 5q15 loss, 12p13.31 gain, and absence of 16p13.3 gain were significantly correlated with worse OS and RFS (p = 0.019 and 0.0027, respectively). CONCLUSIONS: As the target genes in these loci, NR2F1 (5q15), TNFRSF1A (12p13.31), and ABCA3 (16p13.3) were examined. 5q15 loss, 12p13.31 gain, and absence of 16q13.3 gain were potential indicators of high-risk recurrence and aggressive clinical behavior of pN0 invasive breast cancers.

Expanded acceptance of acute exacerbation of nonspecific interstitial pneumonia, including 7 additional cases with detailed clinical pathologic correlation.

Acute exacerbation is uncommonly diagnosed in patients with nonspecific interstitial pneumonia (NSIP) and its pathologic features have received relatively little attention compared to idiopathic pulmonary fibrosis. We retrospectively studied 14 consecutive cases of histopathologically proven NSIP by surgical lung biopsy. The diagnosis of acute exacerbation was confirmed clinically. We analyzed whether four reported pathologic features, including organizing pneumonia lesion, alveolar hemorrhage, many fibroblastic foci, and focal hyaline membranes were present and suggestive of acute exacerbation of NSIP or not. Acute exacerbation in patients with NSIP was diagnosed in 8 cases, while the remaining 6 cases were diagnosed as clinically stable. Seven cases of organizing pneumonia lesion, 7 of alveolar hemorrhage, 6 of many fibroblastic foci, and 3 of focal hyaline membranes were identified as the main pathologic components in patients with acute exacerbation. Organizing pneumonia lesion and many fibroblastic foci were identified in 2 and 3 stable cases, respectively. Having more than two components was significantly associated with acute exacerbation. Evaluation of lung biopsies with NSIP for organizing pneumonia lesions, alveolar hemorrhage, many fibroblastic foci, and focal hyaline membranes may be useful to predict the possibility of acute exacerbation.

Hypersensitivity Pneumonitis A Perspective From Members of the Pulmonary Pathology Society.

CONTEXT: - Hypersensitivity pneumonitis (HP) is a lung disease that develops in susceptible individuals after inhalational exposure to an organic antigen or chemical compound. Pathogenesis is attributed to a combination of type III (immune complex-mediated) and type IV (delayed) hypersensitivity reactions to the inciting agent. OBJECTIVE: - To provide an overview of the current status of the medical literature regarding hypersensitivity pneumonitis. DATA SOURCES: - A literature search was performed using PubMed and Google search engines. The terms "hypersensitivity pneumonitis" and "extrinsic allergic alveolitis" were used, with the search starting on January 9, 2017, and concluding March 8, 2017. CONCLUSIONS: - As a pathologist, it is important to consider hypersensitivity pneumonitis when examining lung specimens because it is often clinically and pathologically overlooked. Recognizing the often subtle findings and correlating them with the patient's history or suggesting a thorough clinical investigation of potential exposures can be of help in identifying the underlying condition so that the patient can be appropriately managed.

[A Case of Squamous Cell Carcinoma in Bladder Diverticulum Producing Granulocyte Colony Stimulating Factor].

We report a rare case of squamous cell carcinoma (SCC) in bladder diverticulum producing granulocyte colony stimulating factor (G-CSF). A 59-year-old man complaining of hematuria and right hip pain was admitted with a large cancer in the bladder diverticulum. His laboratory data showed leukocytosis of 20,100/ µ l (neutrophils : 92%) with an elevated G-CSF of 76. 6 pg/ml in the peripheral blood. After neoadjuvant chemotherapy (gemcitabine and cisplatin), radical cystectomy was performed to normalize serum leukocytosis and G-CSF. Histopathological diagnosis was G-CSF-producing SCC pT4N0. He appeared with left pelvic lymph node metastasis and right pulmonary metastasis 3 months after surgery. Therefore, he was treated with four courses of combination chemotherapy (paclitaxel, ifosfamide and nedaplatin) and radiation therapy at left pelvic lymph node metastasis. Computed tomography after these treatments showed complete response. The patient is alive with no evidence of tumor 16 months after surgery.

[A Case of Solitary Adrenal Metastasis from Rectal Cancer Treated by Adrenalectomy after Preoperative Chemotherapy].

Adrenal metastasis from colorectal cancer occurs in the presence of multiple synchronous metastases at other sites. We report a case of heterochronous solitary adrenal metastasis from rectal cancer. A 55-year-old man underwent anterior resection with D3 lymph node dissection for rectal cancer. The pathological stage of the tumor was III b, and adjuvant chemotherapy with mFOLFOX6 was administered for 6 months. Eighteen months after surgery, abdominal computed tomography(CT) revealed right solitary adrenal metastasis. His tumor marker levels were considerably elevated; therefore, he received preoperative chemotherapy with FOLFIRI plus bevacizumab(BV). After preoperative chemotherapy, his tumor marker levels decreased, and CT and FDG-PET/CT did not uncover any other metastatic lesions. The patient was diagnosed with solitary adrenal metastasis, and right adrenalectomy was performed. Histological examination confirmed the tumor to be adrenal metastasis from rectal cancer, and the histopathological Grade was 2. The patient received adjuvant chemotherapy with mFOLFOX6, and he is alive 7 months after adrenalectomy without evidence of recurrence. Adrenalectomy is recommended for solitary adrenal metastasis from colorectal cancer. Additionally, adrenalectomy after preoperative chemotherapy is an effective strategy for patients with solitary adrenal metastasis and high tumor marker levels.

Clinico-pathological analysis referring hemeoxygenase-1 in acute fibrinous and organizing pneumonia patients.

Acute fibrinous and organizing pneumonia (AFOP) is a very rare pathological entity of lung injury characterized by intra-alveolar fibrin balls. Hemeoxygenase (HO) -1 is a cytoprotective enzyme against oxidative stress and inflammation. It is known to be expressed in the alveolar macrophages in the healthy adults and overexpressed in other various lung cells of the lung injury patients. We experienced two cases of subacute form AFOP for these 10 years and reviewed clinico-pathological characteristics. The average age was 62 years old and both were male. The etiology of both cases was idiopathic. The average PaO2/FIO2 ratio was 274.5 ± 84.1. The average levels of C-reactive protein and surfactant protein - A of the serum were elevated to 19.8 ± 6.3 mg/dL and 67.6 ± 15.8 ng/mL, respectively. Serum sialylated carbohydrate antigen levels were normal in both cases. The characteristic radiographic findings were bilateral consolidations and ground glass opacities. Lung biopsy specimens revealed fibrin balls and alveolitis with abundant cellular HO-1 expression. Steroid response was excellent and the pulmonary involvements absolutely disappeared for about 3 months.

High levels of DJ-1 protein and isoelectric point 6.3 isoform in sera of breast cancer patients.

In patients with cancer and Parkinson's disease, the DJ-1 protein may be secreted into the serum during the impaired response of the underlying cell-protective mechanisms. In order to determine the clinical significance of DJ-1 protein in the sera of breast cancer patients, we examined blood samples from a breast cancer group (n = 180) and a non-cancerous control group (n = 300). Higher levels of DJ-1 were detected in the breast cancer group (mean level, 42.7 ng/mL) than the control group (28.3 ng/mL) by ELISA (P = 0.019). Higher DJ-1 levels were significantly associated with advanced clinical grade, according to the TNM classification, negative hormone receptor status, and high Ki-67 labeling index, of biopsied materials; samples showed low DJ-1 protein expression despite upregulated DJ-1 mRNA. DJ-1 isoforms could be detected clearly in 17 blood samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel electrophoresis and immunoblot analysis. The isoform at the pI of 6.3 showed the highest intensity in all 11 cancer cases. Conversely, in the 6 non-cancerous cases, isoforms other than the pI 6.3 isoform were highly expressed, and there was a significant difference in the isoform pattern between breast cancer cases and controls (P = 0.00025). These data indicate that high levels of DJ-1, probably of isoform at pI 6.3, is a candidate serum marker of breast cancer.

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.

Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

Pleuroparenchymal fibroelastosis as a series of airway complications associated with chronic graft-versus-host disease following allogeneic bone marrow transplantation.

We herein report the case of a 31-year-old woman who presented with bilateral upper lobe volume loss and pleural irregularities with hilar retraction. She had undergone allogeneic bone marrow transplantation (BMT) for the treatment of acute lymphoblastic leukemia nine years earlier. A surgical lung biopsy showed pleural thickening and subpleural alveolar collapse and fibrosis, consistent with a diagnosis of pleuroparenchymal fibroelastosis (PPFE). Antecedent sicca syndrome and the absence of other causes of fibroelastosis suggested that these abnormalities were associated with chronic graft-versus-host disease (cGVHD). PPFE as a late, noninfectious complication is rare; however, the present case suggests a new class of BMT-related pulmonary complications associated with cGVHD.

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.

Fatty acid synthase overexpression in adult testicular germ cell tumors: potential role in the progression of non-seminomatous germ cell tumors.

Overexpression of fatty acid synthase (FASN), which is a key enzyme responsible for the endogenous synthesis of fatty acids, and its association with multistep progression have been demonstrated in various human malignant tumors. We aimed to clarify the potential role of FASN overexpression in the development and progression of adult testicular germ cell tumors (TGCTs). From the primary sites of a cohort of 113 TGCT cases, we obtained 221 histological components: 53 intratubular germ cell neoplasias, unclassified (IGCNUs), 84 seminomas, 32 embryonal carcinomas, seven choriocarcinomas, 21 yolk sac tumors, and 24 teratomas. Samples were analyzed for overexpression of FASN by immunohistochemistry. Intensities of immunoreactivity and the fraction of positive cells were classified into each four categories (intensity, 0 to 3; fraction, 0-10 % = 1, 11-50 % = 2, 51-80 % = 3, and >80 % = 4). The overall score was determined by multiplication of both scores and overall scores greater than 6 were considered FASN overexpression. On a component basis, FASN overexpression was detected in 8 % of seminomas but not in IGCNUs (0 %) and was detected frequently in non-seminomatous germ cell tumors (NSGCTs) (88 % of embryonal carcinomas, all choriocarcinomas, 81 % of yolk sac tumors, and 54 % of teratomas). There were no cases of a mixed tumor (i.e., a tumor with multiple histological components) that overexpressed FASN in seminoma components but not in co-existing NSGCT components, suggesting sequential progression. Our immunohistochemical data suggest that FASN overexpression occurs as a late event during the progression from IGCNUs/seminomas to NSGCTs.