Publications by authors named "Masato Nakaguro"

49 Publications

Predictors of failure of mitral valve repair using artificial chordae.

Ann Thorac Surg 2021 May 19. Epub 2021 May 19.

Department of Cardiac Surgery, Nagoya University Graduate School of Medicine.

Background: We investigate predictors of failure of mitral valve repair (MVr) using expanded polytetrafluoroethylene (ePTFE) and durability of them in the long-term period in single institution.

Methods: Four hundred twenty-one consecutive patients with primary mitral valve disease underwent MVr using artificial chordae (group A: n=304) and suture repair (group S: n=117) at our institution from January 2002 to April 2020. A comparison study was performed to examine the long-term outcomes, re-operation rate and risk factors for re-operation.

Results: One hospital death and 5 late deaths occurred in group S, and 20 late deaths occurred in group A. The re-operation rates were similar [group A; n=8 (2.6%), group S; n=6 (5%)]. The major cause of re-operation was ruptured ePTFE (CV-4: n=1, CV-5: n=6) in group A, and suture rupture in group S. Re-operation was performed after a median period of 88 months for ruptured ePTFE, and 26 months for group S. The rate of ePTFE rupture was 1.8% with CV5 and 0.2% with CV4. Risk factors for re-operation included post-operative arrhythmia, urgent operation, no annular-ring, ruptured ePTFE and suture rupture. The rates of freedom from re-operation and actuarial mitral valve survival rates at 5, 10, and 15 years were 99%, 95%, and 93% and 96%, 91%, and 89%, respectively, in group A, and 96%, 91%, and 91% and95%, 94%, and 94% in group S.

Conclusions: The long-term surgical outcomes of MVr using both techniques were feasible. Over the long-term, the ePTFE rupture rate of CV-5 was higher than that of CV-4.
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.084DOI Listing
May 2021

Intraductal Carcinoma of the Salivary Gland with NCOA4-RET: Expanding the Morphologic Spectrum and an Algorithmic Diagnostic Approach.

Hum Pathol 2021 May 12. Epub 2021 May 12.

Department of Pathology, Massachusetts General Hospital; Department of Otolaryngology, Massachusetts Eye and Ear; Department of Pathology, Harvard Medical School, Boston, MA, USA. Electronic address:

Following the publication of the 2017 WHO Classification of Head and Neck Tumours, there has been increasing interest in the classification of newly categorized intraductal carcinomas. Intraductal carcinoma (IC) is an indolent tumor, typically arising in the parotid gland, with an intact myoepithelial layer and a cystic, papillary, often cribriform architecture. Early studies of IC identified a heterogeneous group of molecular alterations driving neoplasia, and recent studies have defined three primary morphological/immunohistochemical variants, subsequently linking these morphologic variants with defined molecular signatures. While studies to date have pointed toward distinct molecular alterations following histological classification, this study used a novel approach, focusing primarily on six cases of IC with NCOA4-RET gene rearrangement as determined by next-generation sequencing, and describing the spectrum of clinicopathologic findings within that molecularly-defined group, among them a unique association between the NCOA4-RET fusion and hybrid variant IC and the first case of IC arising in association with a pleomorphic adenoma. RET-rearranged IC show histological and immunohistochemical overlap with the more widely recognized secretory carcinoma, including low-grade morphology, a lumen-forming or microcystic growth pattern, and co-expression of S100, SOX10, and mammaglobin, findings undoubtedly leading to misdiagnosis. Typically regarded to have ETV6-NTRK3 fusions, secretory carcinomas may alternatively arise with RET fusions as well. Adding our cohort of 6 NCOA4-RET fusion-positive IC compared with 4 cases of secretory carcinoma with ETV6-RET fusions and a single case of fusion-negative IC with salivary duct carcinoma-like genetics, we propose a diagnostic algorithm that integrates histological elements, including atypia and invasiveness, and the likelihood of specific molecular alterations to increase diagnostic accuracy in what can be a very subtle diagnosis with important clinical implications.
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http://dx.doi.org/10.1016/j.humpath.2021.05.004DOI Listing
May 2021

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Head Neck Pathol 2021 May 12. Epub 2021 May 12.

Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.
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http://dx.doi.org/10.1007/s12105-021-01331-7DOI Listing
May 2021

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma.

Pathol Int 2021 Apr 5. Epub 2021 Apr 5.

Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients' antitumor immune response.
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http://dx.doi.org/10.1111/pin.13099DOI Listing
April 2021

Epithelial-Myoepithelial Carcinoma.

Surg Pathol Clin 2021 Mar 6;14(1):97-109. Epub 2021 Jan 6.

Department of Anatomic Pathology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, Japan. Electronic address:

Epithelial-myoepithelial carcinoma is an uncommon low-grade salivary gland carcinoma. It is classically characterized by biphasic tubular structures composed of inner eosinophilic ductal cells and outer clear myoepithelial cells. In addition, epithelial-myoepithelial carcinoma sometimes shows various histologic features, including a cribriform pattern, basaloid appearance, and sebaceous differentiation. Because clear myoepithelial cells are also noted in other benign and malignant salivary gland tumors, the histologic variety and similarity with other tumor entities make the diagnosis of epithelial-myoepithelial carcinoma challenging. A recent analysis revealed that HRAS hotspot point mutations are specifically identified in epithelial-myoepithelial carcinoma and the assessment of given genes facilitate the correct diagnosis.
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http://dx.doi.org/10.1016/j.path.2020.10.002DOI Listing
March 2021

The Diagnostic Utility of RAS Q61R Mutation-specific Immunohistochemistry in Epithelial-Myoepithelial Carcinoma.

Am J Surg Pathol 2021 Jul;45(7):885-894

Departments of Anatomic Pathology.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety and overlap of histologic features with other salivary gland tumors, there are broad differential diagnoses. The HRAS Q61R mutation has been reported to be frequent in and specific to EMC. We evaluated the usefulness of RAS Q61R mutant-specific immunohistochemical (IHC) staining for detecting this genetic alteration in EMC. We investigated 83 EMC cases and 66 cases of salivary gland tumors with an EMC-like component, including pleomorphic adenoma, adenoid cystic carcinoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. Sanger sequencing was performed for HRAS, KRAS, and NRAS. The diffuse and membranous/cytoplasmic RAS Q61R IHC expression was observed in 65% of EMC cases, in which all cases harbored the HRAS Q61R mutation. IHC-positive cases were present only in de novo EMCs (54/76 cases, 71%) but not in EMCs ex pleomorphic adenoma. The immunoreactivity was almost always restricted to the myoepithelial cells. Conversely, all EMC cases lacking the HRAS Q61R mutation were negative on IHC. In addition, only 3% of EMC-like tumors showed the abovementioned immunopositivity. None of the cases examined carried KRAS or NRAS mutations. IHC for RAS Q61R is highly sensitive and specific for detecting the HRAS Q61R mutation in EMC. Since significant immunopositivity was almost exclusively identified in nearly two thirds of EMCs but seldom in the histologic mimics, the IHC of RAS Q61R is a useful tool for diagnosing EMC in general pathology laboratories.
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http://dx.doi.org/10.1097/PAS.0000000000001673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192334PMC
July 2021

Sialadenoma Papilliferum of the Bronchus: An Unrecognized Bronchial Counterpart of the Salivary Gland Tumor With Frequent BRAF V600E Mutations.

Am J Surg Pathol 2021 05;45(5):662-671

Departments of Anatomic Pathology.

Sialadenoma papilliferum (SP) is a rare benign tumor of the salivary glands, and only 3 unequivocal cases of SP arising in the bronchus have been reported. We herein describe the histomorphologic and molecular features of 4 bronchial SP cases and discuss the differential diagnosis of this entity and the relationship with its clinicopathologic mimics, in particular, glandular papilloma and mixed squamous cell and glandular papilloma (GP/MP). We encountered 2 male and 2 female patients with bronchial SP (mean: 66.8 y old). All 4 tumors arose in the central bronchus and were characterized by a combination of surface exophytic endobronchial papillary proliferation and a submucosal multicystic component with complex architecture. The neoplastic epithelium consisted predominantly of nonciliated stratified columnar cells with ciliated, squamous, and mucinous cells present focally. While 2 tumors (50%) harbored a BRAF V600E mutation by molecular and immunohistochemical analysis, similar to GP/MP, no KRAS, HRAS, AKT1, or PIK3CA mutations were detected in any of the cases. Two patients were treated with limited resection, while 2 patients underwent lobectomy based on the diagnosis of adenocarcinoma or possible squamous cell carcinoma in situ in the preoperative biopsy. All survived without recurrence or metastasis for 23 to 122 months after treatment. SP can develop in the central bronchus as the bronchial counterpart of the salivary gland tumor and should be considered in the differential diagnosis of endobronchial tumors. In addition, some histologic resemblance and frequent BRAF V600E mutation raise the possibility of SP and GP/MP being on the same disease spectrum.
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http://dx.doi.org/10.1097/PAS.0000000000001657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035241PMC
May 2021

Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system.

Cancer Sci 2021 Mar 2;112(3):1184-1195. Epub 2021 Feb 2.

Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.
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http://dx.doi.org/10.1111/cas.14790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935776PMC
March 2021

Solitary fibrous tumor/hemangiopericytoma treated with temozolomide plus bevacizumab: a report of four cases and literature review.

Nagoya J Med Sci 2020 Nov;82(4):631-644

Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare tumor derived from mesenchymal tissue. Although standard chemotherapy for SHT/HPC has not been established, temozolomide plus bevacizumab (TMZ+Bev) therapy for SFT/HPC has been reported. The effectiveness and safety of TMZ+Bev (temozolomide 150 mg/m orally on days 1-7 and days 15-21 and bevacizumab 5 mg/kg intravenously on day 8 and day 22 on a 28-day cycle), which was administered from December 2013 until April 2019 to four patients with SFT/HPC, were retrospectively analyzed. Four patients with SFT/HPC received TMZ+Bev. The age of the patients ranged from 41 to 75 years. Two were male, and the primary tumor sites were the meninges in three patients and the pleura in one. One achieved partial response; the others, stable disease (SD). The progression-free survival time ranged from 9.4 to 29.6 months according to RECIST v1.1. One patient died 59 months after using TMZ+Bev, and the others survived for 17 to 64 months. All patients experienced Grade 3 or higher lymphopenia, and three had Grade 3 or higher leukopenia and neutropenia. One patient subsequently received doxorubicin; another, pazopanib. TMZ+Bev therapy for SFT/HPC is safe and effective for maintaining long-term SD.
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http://dx.doi.org/10.18999/nagjms.82.4.631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719452PMC
November 2020

Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables.

Pathol Int 2021 Jan 1;71(1):33-41. Epub 2020 Dec 1.

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1.
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http://dx.doi.org/10.1111/pin.13048DOI Listing
January 2021

Fine needle aspiration of salivary gland carcinomas with high-grade transformation: A multi-institutional study of 22 cases and review of the literature.

Cancer Cytopathol 2021 Apr 19;129(4):318-325. Epub 2020 Nov 19.

Departments of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: High-grade transformation (HGT) is a rare process whereby conventional low- to intermediate-grade salivary gland carcinomas (SGC) transform into high-grade, poorly or undifferentiated malignancies with focal or complete loss of their conventional histomorphologic features. Because tumors with HGT are associated with a worse prognosis than their conventional counterparts, preoperative recognition of HGT may be of benefit for optimal patient management. Using a multi-institutional approach, we describe the largest fine needle aspiration (FNA) cohort of salivary gland carcinomas with HGT.

Methods: The archives of 9 large academic medical centers were searched, and 22 cases of SGC with HGT were identified by surgical excision accompanied by preoperative FNA. Clinical and cytomorphologic features were retrospectively reviewed.

Results: The male-to-female ratio was 14:8, and the mean patient age was 60.2 years. The average tumor size was 3.6 cm, and 19 cases were from the parotid gland. Acinic cell carcinoma with HGT was the most common tumor subtype, comprising 12 cases with HGT, followed by adenoid cystic carcinoma, secretory carcinoma, and other subtypes. Eighteen cases were classified as malignant; however, a specific diagnosis of HGT was not made. Sixteen cases contained a high-grade cytologic component, and 7 cases had a mixture of both conventional and high-grade components retrospectively.

Conclusions: SGC with HGT should be considered in the differential diagnosis of a salivary gland aspirate exhibiting high-grade cytomorphologic features. The presence of distinct tumor populations, conventional and high-grade, should prompt consideration of HGT, especially when the conventional component is acinic cell carcinoma or adenoid cystic carcinoma.
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http://dx.doi.org/10.1002/cncy.22388DOI Listing
April 2021

Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations.

Histopathology 2020 Nov 1. Epub 2020 Nov 1.

Department of Anatomical Pathology, Tokyo Medical University, Tokyo, Japan.

Aims: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.

Methods And Results: Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.

Conclusions: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.
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http://dx.doi.org/10.1111/his.14296DOI Listing
November 2020

Microsecretory adenocarcinoma of the hard palate: A case report of a recently described entity.

Pathol Int 2020 Oct 20;70(10):781-785. Epub 2020 Jul 20.

Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Japan.

We report a case of microsecretory adenocarcinoma of the hard palate. The patient is a 37-year-old woman with a 15 mm submucosal tumor, which was incidentally found by her primary care dentist, in her hard palate. Preoperative magnetic resonance imaging revealed a tumor exhibiting high signal on T2-weighted image, which was gradually enhanced on dynamic study. Histologically, the tumor border was ill-defined without fibrous capsule and adjoined minor salivary gland with permeative infiltration at the tumor periphery. The tumor comprised intercalated duct-like cells with polygonal narrow eosinophilic to clear cytoplasm and small, uniform oval nuclei. These cells formed small infiltrative microcysts, tubules and fascicular cords collecting pale basophilic secretions and small vacuoles setting in an abundant fibromyxoid stroma. The tumor cells were positive for CK AE1+AE3, S-100 protein, and p63, while are completely negative for p40, alpha-SMA, and calponin. The MEF2C-SS18 fusion was identified by reverse transcriptase-polymerase chain reaction followed by Sanger sequencing. The combination of characteristic histology, immunophenotype, and presence of MEF2C-SS18 fusion indicated the diagnosis of microsecretory adenocarcinoma of the hard palate, an entity described only recently. Post-operative course was uneventful and there was no evidence of disease at 4 months after surgery.
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http://dx.doi.org/10.1111/pin.12987DOI Listing
October 2020

The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan.

Int J Clin Oncol 2020 Oct 1;25(10):1774-1785. Epub 2020 Jul 1.

Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-ku, Nagoya, 467-8601, Japan.

Background: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified.

Methods: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists.

Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy.

Conclusions: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.
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http://dx.doi.org/10.1007/s10147-020-01731-9DOI Listing
October 2020

Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis.

Int J Surg Pathol 2020 Dec 26;28(8):844-849. Epub 2020 May 26.

13056Shinshu University, Matsumoto, Japan.

Background.: Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4 plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD.

Methods.: We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists.

Results.: Although mean values for IgG cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; [IgG] = 0.988 + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent.

Conclusion.: AC-IgG could replace IgG to count IgG cells because of its lower Cv.
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http://dx.doi.org/10.1177/1066896920924781DOI Listing
December 2020

Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment.

Cancer Cytopathol 2020 10 18;128(10):693-703. Epub 2020 May 18.

Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.

Salivary duct carcinoma (SDC) is an aggressive subtype of primary salivary gland carcinoma, often with an advanced stage at presentation and high rates of metastasis and recurrence. It most commonly arises in the parotid gland of older men and microscopically resembles high-grade breast ductal carcinoma. While 50 years have lapsed since the first report of this entity, recent intensive studies have shed light on its biologic, genetic, and clinical characteristics. The diagnosis of SDC is aided by the immunohistochemical expression of androgen receptor (AR) coupled with its characteristic histomorphology. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma, and ancillary studies using cell block material can facilitate the specific diagnosis of SDC. In surgical specimens, certain histologic features are important prognostic factors, including nuclear pleomorphism, mitotic counts, vascular invasion, and the morphology at the invasion front. Several clinical studies have shown promising results using targeted therapy for AR and human epidermal growth factor receptor 2 (HER2), and the latest version of the National Comprehensive Cancer Network guidelines recommends the evaluation of AR and HER2 status before treatment. Recent molecular analyses have revealed multiple heterogeneous alterations in well-known oncogenes and tumor suppressor genes, including TP53, HRAS, PIK3CA, PTEN, and BRAF. Clinical trials of drugs targeting these genes may broaden the treatment options for SDC in the near future.
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http://dx.doi.org/10.1002/cncy.22288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541685PMC
October 2020

A familial case of alveolar capillary dysplasia with misalignment of the pulmonary veins: the clinicopathological features and unusual glomeruloid endothelial proliferation.

Diagn Pathol 2020 May 9;15(1):48. Epub 2020 May 9.

Department of Diagnostic Pathology, Kyoto University Hospital, 54 Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare disorder of pulmonary vascular abnormality with persistent pulmonary hypertension of the newborn. The symptom usually presents within hours after birth, leading to an early demise. Heterozygous de novo point mutations and genomic deletions of the FOXF1 (forkhead box F1) gene or its upstream enhancer have been identified in most patients with ACD/MPV. Most cases of ACD/MPV are sporadic; however, familial cases are also reported in 10% of patients.

Case Presentation: We herein report a case of familial ACD/MPV that showed unusual glomeruloid proliferation of endothelial cells. In this family, three of the four siblings died within two to 3 days after birth because of persistent pulmonary hypertension and respiratory failure. Only the second child remains alive and healthy. An autopsy was performed for the third and fourth children, resulting in a diagnosis of ACD/MPV based on the characteristic features, including misalignment of smaller pulmonary veins and lymphangiectasis. In both of these children, glomeruloid endothelial proliferation of vessels was noted in the interlobular septa. The vessels were immunohistochemically positive for D2-40, CD31, Factor VIII, and ERG, suggestive of differentiation for both lymphatic and blood vessels.

Conclusions: Unusual glomeruloid endothelial proliferation was observed in a familial ACD/MPV case. This histologic feature has not been described previously in ACD/MPV or any other pulmonary disease. Although the histogenesis of this histologic feature is unclear, this finding may suggest that ACD/MPV is a compound vascular and lymphovascular system disorder that exhibits various histologic features.
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http://dx.doi.org/10.1186/s13000-020-00972-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211333PMC
May 2020

The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma.

Virchows Arch 2020 Aug 26;477(2):291-299. Epub 2020 Feb 26.

Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.

Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)-positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism-related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.
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http://dx.doi.org/10.1007/s00428-020-02777-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371671PMC
August 2020

Enhanced performance of the Milan System for Reporting Salivary Gland Cytopathology: Point of view from an Asian country.

Cancer Cytopathol 2020 05 5;128(5):305-306. Epub 2020 Feb 5.

Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1002/cncy.22244DOI Listing
May 2020

Central pathology review of salivary gland adenoid cystic carcinoma.

Head Neck 2020 08 23;42(8):1721-1727. Epub 2020 Jan 23.

Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Background: To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (AdCC).

Methods: Surgically resected salivary gland tumors diagnosed as AdCC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re-evaluation.

Results: After the review, the AdCC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants.

Conclusions: A significant proportion of AdCC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating AdCC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.
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http://dx.doi.org/10.1002/hed.26081DOI Listing
August 2020

Giant cell myocarditis with central diabetes insipidus: A case report.

J Cardiol Cases 2020 Jan 10;21(1):8-11. Epub 2019 Sep 10.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

A 51-year-old male, previously diagnosed with central diabetes insipidus due to lymphocytic hypophysitis, presented with fever and dyspnea for 1 week. On arrival, he exhibited hypotension (85/60 mmHg) and sinus tachycardia (110 bpm). His electrocardiogram revealed mild ST elevation on V2-V4. Echocardiography indicated a near-normal (50%) left ventricular ejection fraction (LVEF), although the inferior wall of the left ventricle exhibited severe hypokinesis. Fulminant myocarditis and circulatory insufficiency were suspected, and treatment with dobutamine, 3 μg/kg/min, was started. His LVEF gradually decreased to 20%. On day 17, he developed cardiogenic shock due to ventricular tachycardia and underwent peripheral venous-arterial extracorporeal membrane oxygenation and intra-aortic balloon pumping. Although he did not exhibit polyuria, intravenous vasopressin infusion (0.5 U/h) was performed to maintain normonatremia. Endomyocardial biopsy results revealed the infiltration of scattered giant cells (GCs) and extensive lymphocytes. Despite immunosuppressive therapy (methylprednisolone and cyclosporine), his cardiac function did not recover. On day 36, he received a biventricular assist device; however, he died on day 47 due to the progression of sepsis and multiple organ failure. We speculate that a deficient expression of programmed cell death protein-1 was the cause of both GC myocarditis and lymphocytic hypophysitis. <: We describe a fatal case of fulminant giant cell myocarditis complicated by central diabetes insipidus due to lymphocytic hypophysitis. Normonatremia was maintained with intravenous vasopressin 0.5 U/h, and circulatory status was maintained with mechanical circulatory support. We speculate that T-cell programmed cell death protein 1 dysregulation was the common cause of the two disorders.>.
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http://dx.doi.org/10.1016/j.jccase.2019.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951310PMC
January 2020

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry.

Pathol Int 2020 Feb 2;70(2):108-115. Epub 2020 Jan 2.

Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Aichi, Japan.

Although several reports have highlighted neoplastic PD-L1 (nPD-L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV-CHL), with and without Epstein-Barr virus (EBV) association, and highlight the diagnostic utility of PD-L1 (clone SP142) immunohistochemistry. The patients were a 61-year-old male, 45-year-old male, 85-year-old female, and 89-year-old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV-CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed-Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD-L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD-L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing 'confluent' sheets in the diagnostic workup for SV-CHL.
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http://dx.doi.org/10.1111/pin.12888DOI Listing
February 2020

Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases.

Pathol Int 2020 Feb 2;70(2):116-122. Epub 2020 Jan 2.

Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Aichi, Japan.

Composite lymphoma is a well-known diagnostic entity exhibiting the synchronous occurrence of two or more distinct types of lymphomas in the same specimen. Here we report two patients, a 14-year-old female (Case 1) and a 45-year-old male (Case 2), with mediastinal composite lymphoma, comprising nodular sclerosis classic Hodgkin lymphoma (NSCHL) and primary mediastinal large B-cell lymphoma (PMBL). Both patients had a mediastinal mass, and manifested two different histologic components in the same biopsy, one characteristic of NSCHL and the other PMBL. The NSCHL areas included Hodgkin and Reed-Sternberg (HRS) cells with typical immunophenotypic features (CD30-positive and CD20-negative), whereas the sheets of large tumor cells characteristic of PMBL were strongly and uniformly CD20-positive. Interestingly, although both cases showed neoplastic PD-L1 (nPD-L1) positivity on the HRS cells of NSCHL, they differed regarding nPD-L1 expression on the PMBL tumor cells. In Case 1, the nPD-L1-negative PMBL component was anatomically situated outside the NSCHL lesion. On the other hand, in Case 2, the nPD-L1-positive PMBL component was characterized by transitional or continuous areas with the NSCHL component. These findings suggested that nPD-L1 expression may define two subtypes of PMBL that are more similar to or distinct from classic Hodgkin lymphoma.
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http://dx.doi.org/10.1111/pin.12891DOI Listing
February 2020

Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma: Proposal of a Novel Histologic Risk Stratification Model.

Am J Surg Pathol 2020 04;44(4):526-535

Departments of Anatomic Pathology.

Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.
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http://dx.doi.org/10.1097/PAS.0000000000001413DOI Listing
April 2020

Calculating the Tumor Nuclei Content for Comprehensive Cancer Panel Testing.

J Thorac Oncol 2020 01 9;15(1):130-137. Epub 2019 Oct 9.

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan. Electronic address:

Comprehensive genetic panel testing generally requires that the analyzed tissues have a percent tumor nuclei (%TN) content of 20% or more to achieve assay performance comparable to the validated specifications. Pathologists play a crucial role in ensuring that the optimal results are achieved by accurately assigning %TN content of the available specimens and selecting the best material to submit for sequencing. This study addresses the issues in evaluating %TN, such as intraobserver variability, and examines whether focused training and feedback can improve pathologist performance. Nine referring institution pathologists (all board-certified and working at the core institute and the alignment hospitals under the National Cancer Genome scheme) evaluated 18 tumors that had been subjected to comprehensive genetic panel testing with the FoundationOne CDx assay. The %TN estimates provided by referring institution pathologists were compared with two standards: %TN assigned by the tumor sequencing institution's pathologist (a board-certified pathologist at Foundation Medicine, Inc.) and the computational %TN estimated from the mutant allele frequencies after sequencing was completed. The pathologists generally overestimated %TN in the first pretraining round of the evaluation, and the differences in the averaged %TN from the tumor sequencing institution and computational standards were statistically significant. However, the posttraining second-round results became significantly concordant with the standards. This study suggests that %TN content is empirically overestimated but the evaluation skill can be improved by providing a training and feedback program.
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http://dx.doi.org/10.1016/j.jtho.2019.09.081DOI Listing
January 2020

Fatal case of TAFRO syndrome associated with over-immunosuppression: a case report and review of the literature.

Nagoya J Med Sci 2019 Aug;81(3):519-528

Department of General Medicine/Family & Community Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.

TAFRO syndrome is a novel disease concept characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and a histopathological pattern of atypical Castleman's disease. A 58-year-old man was diagnosed as TAFRO syndrome by clinical and histopathological findings. After receiving intensive immunosuppressive therapy, his thrombocytopenia and anasarca had not improved. He developed complications such as methicillin-resistant , gastrointestinal bleeding, peritonitis caused by , gastrointestinal perforation, and disseminated candidiasis resulting in death. Autopsy revealed disseminated candidiasis and hemophagocytic lymphohistiocytosis, with no evidence of TAFRO syndrome. During treatment, we regarded his lasting thrombocytopenia and anasarca as insufficient control of TAFRO syndrome. However, the autopsy revealed that thrombocytopenia was caused by secondary hemophagocytic lymphohistiocytosis caused by over-immunosuppression. We reviewed the published literature to identify indicators of adequate treatment, which suggested improvement of platelet count and anasarca several weeks after initial therapy. This indicated that we could not depend on the platelet count and anasarca in acute medical care after initial treatment. We should treat TAFRO syndrome based on patients' clinical status and obviate the risk of treatment-related complications caused by over-immunosuppression.
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http://dx.doi.org/10.18999/nagjms.81.3.519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728207PMC
August 2019

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

Histopathology 2020 Feb 1;76(3):411-422. Epub 2019 Dec 1.

Department of Anatomical Pathology, Tokyo Medical University, Tokyo, Japan.

Aims: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN).

Methods And Results: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells.

Conclusion: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.
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http://dx.doi.org/10.1111/his.13990DOI Listing
February 2020

Color information from linked color imaging is associated with invasion depth and vascular diameter in superficial esophageal squamous cell carcinoma.

Dig Endosc 2020 Jan 3;32(1):65-73. Epub 2019 Oct 3.

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan.

Objectives: Accurate diagnosis of invasion depth is important for reliable treatment of esophageal squamous cell carcinoma (ESCC), but it is limited to the muscularis mucosae to slight submucosal invasion (MM/SM1). The diagnostic accuracy of invasion depth is unsatisfactory and remains to be improved. We aimed to investigate the association between the color of the superficial ESCC and invasion depth using linked color imaging (LCI) under light-emitting diode (LED) light sources.

Methods: Lesions diagnosed as superficial ESCC were observed using white light imaging and then by LCI. The color values were calculated using Commission Internationale de l'Eclariage - L*a*b* color space, and the color difference was calculated according to invasion depth. The vascular diameters and vascular angles of the intrapapillary capillary loops were pathologically analyzed. Their correlation with mucosal color was also investigated by LCI.

Results: In all, 52 lesions from 48 patients were analyzed. On the basis of invasion depth, the color difference between the normal mucosa and the lesion was larger in the MM/SM1 or deeper group than in the epithelium and the lamina propria mucosa (EP/LPM) group using LCI (P = 0.025). The vascular diameter was positively correlated with the b* color value (correlation coefficient = 0.302, P = 0.033).

Conclusion: Observation using LCI under LED light sources may improve the endoscopic diagnosis of the invasion depth of superficial ESCC. Further research is needed to validate its usefulness. (UMIN000024615).
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http://dx.doi.org/10.1111/den.13469DOI Listing
January 2020

BK virus-associated viruria and viremia in a patient with lymphangioleiomyomatosis after lung re-transplantation: A case report and review of the literature on BK virus infection post-lung transplantation.

J Infect Chemother 2019 Oct 23;25(10):820-824. Epub 2019 Apr 23.

Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address:

The BK virus (BKV) is a member of the polyomaviridae family of DNA viruses. BKV reactivates under a highly immunosuppressed state and causes renal dysfunction. In renal transplant patients, BKV infection leads to tubular impairment and loss of transplanted kidney grafts. However, few studies have reported on the relationship between BKV and lung transplantation. Adjustment of the dosage of immunosuppressants is needed in some cases, but the treatment method has not been established. Here, we report a case of BKV-associated viruria and viremia in a patient with lymphangioleiomyomatosis (LAM) after lung re-transplantation. A 44-year-old female refractory LAM patient who had undergone lung re-transplantation 3 months earlier was diagnosed with BKV-associated viruria and viremia. Urine cytology indicated decoy cells and the urine and serum polymerase chain reaction test was positive for BKV. As scheduled after re-transplantation surgery, immunosuppressive drugs were progressively reduced. This patient was considered to have experienced spontaneous BKV-associated viremia and viruria. Review of the literature suggested that 17%-42% of BKV-associated viruria cases have been reported after lung transplantation, but cases of BKV-associated nephropathy are rarely reported. Based on the present case, doctors involved in lung transplantation should monitor patients for BKV infection. Decoy cell monitoring by urine cytology is a useful screening method in the follow-up observation after lung transplantation. Early-stage interventions may prevent BKV-associated nephropathy even in patients who have developed BKV viremia, and sirolimus can be administered to patients with histories of BKV infection if they are carefully monitored.
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http://dx.doi.org/10.1016/j.jiac.2019.04.002DOI Listing
October 2019