Kazuhiro Tabata

Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type.

Objectives: MUC16 carries the peptide epitope CA125, which is well known as a marker of ovarian cancer. High serum levels of MUC16 (CA125) have been reported not only in patients with ovarian cancer but also in patients with liver diseases. We evaluated the expression of MUC16 in intrahepatic cholangiocarcinoma-mass forming type (ICC-MF) tissues. Methods: We examined the expression of MUC16 by immunohistochemical analyses using the monoclonal antibody M11 in ICC-MF tissues from 63 patients. To compare the prevalence of each mucin expression by clinicopathological features, appropriate statistical analysis was performed. Results: MUC16 was detected in 48% of samples (30/63). After adjusting for the effects of other prognostic factors, multivariate survival analysis revealed that MUC16 expression is a significant independent factor of poor prognosis (p = 0.005). Conclusion: The current results indicate that MUC16 expression is a prognostic factor of poor survival in ICC-MF.

Whole-slide imaging at primary pathological diagnosis: Validation of whole-slide imaging-based primary pathological diagnosis at twelve Japanese academic institutes: Validating whole-slide imaging in Japan

Several reports have demonstrated the use of whole‐slide imaging (WSI) for primary pathological diagnosis, but no such studies have been published from Asia. We retrospectively collected 1070 WSI specimens from 900 biopsies and small surgeries conducted in nine hospitals. Nine pathologists, who participated in this study, trained for the College of American Pathologists guidelines, reviewed the specimens and made diagnoses based on digitized, 20× or 40× optically magnified images with a WSI scanner. After a washout interval of over 2 weeks, the same observers reviewed conventional glass slides and diagnosed them by light microscopy. Discrepancies between microscopy‐ and WSI‐based diagnoses were evaluated at the individual institutes, and discrepant cases were further reviewed by all pathologists. Nine diagnoses (0.9%) showed major discrepancies with significant clinical differences between the WSI‐ and microscopy‐based diagnoses, and 37 (3.5%) minor discrepancies occurred without a clinical difference. Eight out of nine diagnoses with a major discrepancy were considered concordant with the microscopy‐based diagnoses. No association was observed between the level of discrepancy and the organ type, collection method, or digitized optical magnification. Our results indicate the availability of WSI‐based primary diagnosis of biopsies and small surgeries in routine daily practice.

Intratumoral heterogeneity of programmed cell death ligand-1 expression is common in lung cancer

Programmed cell death ligand-1 (PD-L1) expression may predict the response to both programmed cell death-1 and PD-L1 inhibitors in lung cancer. However, the extent of intratumoral heterogeneity of PD-L1 expression, which may cause false negative results, is largely unexplored. We aimed to assess the intratumoral heterogeneity of PD-L1 expression in surgically resected lung cancer specimens by applying a novel method of tissue microarray, namely Spiral Arrays, which enables us to observe the heterogeneity in spiral-shaped tissue cores. Adenocarcinoma and squamous cell carcinoma specimens were obtained from consecutive patients with lung cancer who had undergone surgical resection at Nagasaki University Hospital (Nagasaki, Japan) since 2009. Small cell lung cancer and large cell carcinoma specimens were selected from patients in the same archive who had undergone resection since 1998. Spiral Arrays were constructed of spiral-shaped cores, prepared from representative blocks of each case, which were subjected to immunohistochemistry using an anti-PD-L1 antibody. Each core was divided into 8 segments and each segment was classified as either PD-L1-positive or PD-L1-negative using thresholds of 1.0%, 5.0%, 10.0%, and 50.0%, respectively. In total, 138 specimens were selected, including 60 adenocarcinomas, 59 squamous cell carcinomas, 12 small cell lung cancers, and 7 large cell carcinomas. The majority of specimens with PD-L1-positive segments exhibited heterogeneous expression (i.e., had a mixture of PD-L1-positive and PD-L1-negative segments within a core) irrespective of the threshold (1.0%, 66.7%; 5.0%, 74.4%; 10.0%, 75.8%; and 50.0%, 85.7%]. Large variations in the ratios of PD-L1-positive segments were observed. At least 50.0% of the segments within a core were negative in no fewer than 50.0% (range, 50.0–76.0%) of cases with heterogeneous PD-L1 expression. In conclusion, intratumoral heterogeneity of PD-L1 expression was frequently observed in cases of lung cancer. Thus, multiple tumor biopsy specimens may be needed to accurately determine the PD-L1 expression status.

FDG-PET/CT finding of benign metastasizing leiomyoma of the lung

We report a case of multiple benign metastasizing leiomyoma (BML) lung nodules showing faint or non-avid uptake of F-18 fluorodeoxyglucose (FDG) (respective 1-hour early and 2-hour delayed maximum standardized uptake values; 1.3 or less and 1.2 or less) in a 50-year-old woman with a history of hysterectomy for uterine leiomyoma at the age of 38 years. When multiple lung nodules show faint or non-avid FDG uptake in a patient with a history of hysterectomy for uterine leiomyoma, BML should be included in the differential diagnosis.

Bilobular calcifying fibrous pseudotumor in soleus muscle: a case report

IntroductionCalcifying fibrous pseudotumor is a rare benign soft-tissue lesion composed of fibrous tissue with abundant hyalinized collagen and dystrophic and often psammomatous calcifications. The cause of the disease is unclear but, usually, complete resection of the well-circumscribed tumor is sufficient to avoid recurrence of the disease. Here, we report an unusual case of this rare tumor that presented as two lobulated lesions in the calf muscle.Case presentationThe patient was a 17-year-old Japanese girl who noted a hard mass in her left calf. Magnetic resonance imaging revealed two well-demarcated lobular masses in the soleus muscle, and the tumor was significantly enhanced by contrast medium. Preoperative differential diagnoses included soft-part tumors composed of fibrous tissue. However, making a definite diagnosis was impossible because a lobulated shape is rare for fibrous tumors. Biopsy demonstrated that the mass was a benign tumor composed of collagen-rich, hyalinized fibrosclerotic tissue. We performed marginal resection of the two nodules, including the fibrous tissue that connected them. Immunohistochemistry was positive for factor XIIIa and negative for anaplastic lymphoma kinase-1. These findings were helpful to distinguish calcifying fibrous pseudotumor from inflammatory myofibroblastic tumor. There was no sign of recurrence at 30 months after surgery.ConclusionTo the best of our knowledge, this is the first case of bilobular calcifying fibrous pseudotumor that developed in an extremity. As described in the previous literature, simple excision was sufficient for the treatment of calcifying fibrous pseudotumor with two lobules.

Anti-glycyl tRNA synthetase antibody associated interstitial lung disease without symptoms of polymyositis/dermatomyositis.

To the Editor: The anti-aminoacyl tRNA synthetase (ARS) antibody syndrome has large association with interstitial lung disease (ILD). The ARSs are a set of cellular enzymes, each of which catalyzes the formation of aminoacyl tRNA from a specific amino acid and its cognate tRNA. They can be found in; 25–35% of patients with chronic inflammatory muscle disorders, polymyositis (PM) and dermatomyositis (DM). Autoantibody to glycyl tRNA synthase (anti-EJ) is a form of eight anti-ARS antibodies identified in patients with PM/DM. Each of these anti-ARS antibodies has been reported to be associated with a similar syndrome, anti-synthetase syndrome, characterized by myositis with a high frequency of interstitial lung disease (ILD) (50–80%), arthritis (50–90%), and skin lesions of the fingers referred to as ‘mechanic’s hands’ (70%). Among those symptoms, ILD is the most serious life-threatening complication. Some cases of ILD with antiARS-antibody were reported to have no symptoms of myositis. The similarity of clinical features in patients with different anti-ARS antibodies is known, but some reports indicated that there are certain differences in clinical symptoms associated with each of the anti-ARS antibodies. Among eight anti-ARS antibodies, the most common antibody in all patients is anti-Jo-1 (35%). Anti-EJ positive patients are fewer (5–20%), but for the cases with ILD, anti-EJ is the most common antibody (20–35%). Although pulmonary manifestations and radiological findings of ILD in patients with anti-EJ have been reported, no reports have described the pathological features. In this report we describe the radiological and pathological features of an anti-EJ antibody positive patient with ILD, who had the no symptoms of PM/DM. A 56-year-old woman presented progressive nonproductive cough and dyspnea on exertion, with Medical Research Council dyspnea scale of grade 2, for 3 months. Her X-ray showed abnormal shadows. She was a neversmoker and had no significant medical history. She had no other environmental risk factors for respiratory disease except for the use of feather comforter. She was admitted to the hospital for a detailed assessment of her respiratory problem. On physical examination, fine crackles were heard on chest auscultation. Though Raynaud’s phenomena, arthralgia, morning stiffness and xerostomia were found, they didn’t fulfill the diagnostic criteria of any certain connective tissue disease. The blood gas analysis showed a mild hypoxia. The C-reactive protein level was elevated (2.90 mg/dL). The serum levels of Krabs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) were increased (1045 U/mL and 149.6 ng/mL, respectively). The patient’s serum were positive for anti EJ antibody, but negative for antinuclear antibody, other types of anti-ARS antibodies, and other autoantibodies suggesting autoimmune disorders. Pulmonary function test showed slight respiratory disability and diffusion function disorder. Bronchoalveolar lavage (BAL) fluid with differential cell counts were performed in left B5. The total cell number was 5.69 × 10/mL, and lymphocytes dominated at 45% in which the CD4/8 ratio was as low as 0.19. Sets of chest X-ray and high resolution computed tomography (HRCT) were obtained on admission and 2 months after the biopsy. Chest X-ray on admission revealed infiltrative shadows in the bilateral lung(Fig. 1a) and HRCT showed diffuse ground-glass opacities and areas of consolidation along the bronchovascular bundles predominantly in the lower lobes (Fig. 1c) After a video-assisted thoracic surgical (VATS) biopsy, due to rapid progression of the dyspnea, the patient was treated with methylprednisolone 1 g/day for 3 days followed by 40 mg/day of prednisolone with Cyclosporine A, 150 mg/day, for 22 days. Due to the significant improvement of respiratory symptoms and radiographic abnormality, the patient was discharged 70 days after her admission. No recurrent ILD was identified with 4 months’ follow up. Follow up radiograms after the therapy showed remarkable improvement for both bilateral lung fields (Fig. 1b,d). Video-assisted thoracic surgical (VATS) lung biopsy was performed to the left lower lobe superior segment, S6, and anterior basal segment, S8. Both specimens showed similar histological findings. Under the light microscope, the lesion was characterized by the pattern of nonspecific interstitial pneumonia (NSIP), showing moderate cellular inflammatory cell infiltration and mild increase of fibroblast in the alveolar septa. There was a slight centriacinar accentuation, but basically all areas of the lobule were diffusely affected. No area with complete normal lung was found. In addition to the findings typically seen in ordinary NSIP cases, acute inflammatory processes such as exudative edema in both airspace and alveolar septa, presence of a few organizing pneumonia (OP) foci of Masson body type, scattered airspace fibrin, denudation of the pneumocytes, and enlargement of alveolar Disclosure: None of the authors have any financial and personal relationships with other people or organizations that could inappropriately influence. Pathology International 2014; 64: 148–150 doi:10.1111/pin.12140 bs_bs_banner

Clinical outcome of stage Ia1 squamous cell carcinoma of the uterine cervix and pathological findings of initial conization.

Aim:  The present study investigated the clinical outcome of stage Ia1 squamous cell carcinoma (SCC) of the uterine cervix at a single institute.

Expression of coproporphyrinogen oxidase is associated with detection of upper gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic diagnosis

BACKGROUND 5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer. METHODS Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase. RESULTS Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors. CONCLUSION Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.

Diffuse Alveolar Hemorrhage Developing Immediately after Immunosuppressive Treatments in a Patient with Granulomatosis with Polyangiitis Who Had Pulmonary Nodules

A 65-year-old man was diagnosed with granulomatosis with polyangiitis (GPA) based on the detection of high myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), vasculitis and granulomas in a lung biopsy specimen and crescentic glomerulonephritis in a kidney biopsy specimen. Soon after the initiation of intravenous methylprednisolone pulse therapy (mPSL pulse) and intravenous cyclophosphamide pulse therapy (IVCY), the patient experienced cough and hemoptysis. Based on emerging anemia and bilateral diffuse lung consolidation on computed tomography, we judged that diffuse alveolar hemorrhage (DAH) was complicated by GPA. The patients DAH improved following additional mPSL pulse and IVCY. Physicians should be aware of the possible occurrence of DAH, even when a patients symptoms improve after mPSL pulse and IVCY.

Successful Resection of locally infiltrative Glomus Tumor without pulmonary resection

Highlights • Extracutaneous glomus tumors occurring in the bronchus is very rare.• Two term resections enabled us to make an accurate diagnosis and evaluation.• After bronchoscopic treatment, curative pulmonary resection was performed and preservation of lung function was successful.