Publications by authors named "Toshitaka Nagao"

162 Publications

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

Structural changes in renal arterioles are closely associated with central hemodynamic parameters in patients with renal disease.

Hypertens Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Nephrology, Tokyo Medical University, Tokyo, Japan.

Although central hemodynamics are known to be closely associated with microvascular damage, their association with lesions in the small renal arteries has not yet been fully clarified. We focused on arterioles in renal biopsy specimens and analyzed whether their structural changes were associated with noninvasive vascular function parameters, including central blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV). Forty-four nondiabetic patients (18-50 years of age) with preserved renal function underwent renal biopsy. Wall thickening of arterioles was analyzed based on the media/diameter ratio, and hyalinosis was analyzed by semiquantitative grading. Associations of these indexes (arteriolar wall remodeling grade index (RG index) and arteriolar hyalinosis index (Hyl index)) with clinical variables were analyzed. Multiple regression analyses demonstrated that the RG index was significantly associated with central systolic BP (β = 0.97, p = 0.009), serum cystatin C-based estimated glomerular filtration rate (β = -0.36, p = 0.04), and high-density lipoprotein cholesterol levels (β = -0.37, p = 0.02). The Hyl index was significantly associated with baPWV (β = 0.75, p = 0.01). Our results indicate that aortic stiffness and abnormal central hemodynamics are closely associated with renal microvascular damage in young to middle-aged, nondiabetic kidney disease patients with preserved renal function.
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http://dx.doi.org/10.1038/s41440-021-00656-8DOI Listing
April 2021

High-grade salivary gland carcinoma with the ETV6-NTRK3 gene fusion: A case report and literature review of secretory carcinoma with high-grade transformation.

Pathol Int 2021 Apr 13. Epub 2021 Apr 13.

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

Secretory carcinoma or mammary analog secretory carcinoma is an entity of salivary gland carcinoma that is characterized by the ETV6-NTRK3 gene fusion. Although it is generally considered to be a low-grade malignancy, some cases of secretory carcinoma with high-grade transformation (SCHG) have been reported. We herein describe a case of SCHG composed almost exclusively of the high-grade component. The patient presented with a growing mass in the buccal mucosa and underwent surgery. Tumor cells showing high-grade nuclear atypia were arranged in solid or cribriform nests with comedo-like necrosis. A differential diagnosis included high-grade salivary gland carcinoma, such as salivary duct carcinoma. Immunohistochemically, tumor cells were focally positive for S-100 and negative for mammaglobin and showed nuclear positivity for pan-Trk. A reverse transcription polymerase chain reaction assay showed that the tumor harbored the ETV6-NTRK3 gene fusion. A histological review of microscopic slides of the tumor did not reveal a typical secretory carcinoma component, except for a very focal area. We ultimately diagnosed this tumor as SCHG. This case underscores the importance of recognizing the histological spectrum of SCHG and the utility of pan-Trk immunohistochemistry to detect secretory carcinoma, which may be targeted by tyrosine kinase inhibitors.
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http://dx.doi.org/10.1111/pin.13100DOI Listing
April 2021

Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer.

Sci Rep 2021 Apr 9;11(1):7830. Epub 2021 Apr 9.

Department of Surgery, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

PD-L1 expression is the most useful predictive biomarker for immunotherapy efficacy on non-small cell lung cancer (NSCLC), and CD8+ tumor-infiltrating lymphocytes (CD8+ TILs) play an essential role in the clinical activity of immunotherapy. PD-L1 is found on the exosome's surface, and PD-L1 expressing exosomes can inhibit antitumor immune responses. This study aimed to analyze tumor PD-L1 expression, serum exosomal PD-L1, and CD8+ TILs to investigate anti-PD-1 response and clinicopathological outcomes in NSCLC. One hundred twenty patients with stage I-III NSCLC were enrolled, and serum samples collected during the initial surgery were pooled. The Human CD274/PD-L1 ELISA kit was used to quantify the exosomal PD-L1. Exosomal PD-L1 levels were significantly correlated with tumor PD-L1 levels (p < 0.001) and the number of CD8+ TILs (p = 0.001). Patients with exosomal PD-L1 ≥ 166 pg/mL tended to have a worse RFS than those with < 166 pg/mL in all stage (p = 0.163) and stage I patients (p = 0.116). Seventeen patients exhibited postoperative recurrences and received anti-PD-1 treatment. The disease control rate of patients with exosomal PD-L1 ≥ 166 pg/mL was 100%. The measurement of serum exosomal PD-L1 as a quantitative factor with tumor PD-L1 status may help predict anti-PD-1 response and clinical outcomes in patients with NSCLC.
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http://dx.doi.org/10.1038/s41598-021-87575-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035184PMC
April 2021

Magnetic Resonance Imaging of Orbital Solitary Fibrous Tumors: Radiological-Pathological Correlation Analysis.

J Belg Soc Radiol 2021 Mar 16;105(1):14. Epub 2021 Mar 16.

Tokyo Medical University, JP.

Background: Solitary fibrous tumors (SFTs) are rare and can be misdiagnosed because of their various radiological appearances.

Purpose: To clarify the characteristic MRI findings of SFTs by analyzing their radiological-pathological correlation.

Material And Methods: Nine consecutive patients with SFT who underwent magnetic resonance imaging (MRI) prior to surgery were analyzed. Eight patients underwent contrast-enhanced MRI, and three underwent dynamic MRI. Radiological-pathological correlation analysis, co-occurrence matrix, run-length matrix, and histogram analysis were performed to assess the relationship between pathological findings T1- and T2-weighted images (T1-WI and T2-WI).

Results: All nine lesions ranged in size from 20 to 36 mm. Seven lesions were located in the superior portion of the retrobulbar space found outside of the muscle cone, and two lesions in the inferior portion were located within it. No significant correlation was observed between the amount of collagenous tissue and the qualitative evaluation of the signal on T1-WI and T2-WI. Kurtosis on T2-WI was significantly correlated with the amount of collagenous tissue ( = -0.97, < 0.0001) and endothelial cells ( = -0.49, = 0.0479).

Conclusion: Kurtosis in the histogram analysis on T2WI showed a strong correlation with the amount of collagenous tissue.
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http://dx.doi.org/10.5334/jbsr.2097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977021PMC
March 2021

Use of gadoxetic acid-enhanced MRI to predict the development of postoperative pancreatic fistulas by estimating the degree of pancreatic fibrosis.

Curr Med Imaging 2021 Mar 10. Epub 2021 Mar 10.

Department of Anatomic Pathology, Tokyo Medical University. Japan.

Background: Postoperative pancreatic fistula (POPF) can be life-threatening, and gadoxetic acid-enhanced MRI is routinely performed in patients undergoing pancreatic surgery. However, previous reports have not investigated if gadoxetic acid-enhanced MRI can be used to predict POPF risk.

Objective: This study aims to explore if gadoxetic acid-enhanced MRI can predict pancreatic fibrosis and the need for POPF treatment before surgery.

Method: We retrospectively analyzed gadoxetic acid-enhanced MR images from 142 patients who underwent pancreatic surgery between January 1, 2011, and April 30, 2018. Pre-dynamic signal intensity (SI) and values for portal, transitional, and hepatobiliary phase standardized based on pre-dynamic study values were analyzed. The diameter of the main pancreatic duct (DMPD) was measured, and the degree of pancreatic fibrosis was classified as F0-F3. We defined POPF higher than grade B as significant.

Results: Odds ratios for combinations that led to any degree of fibrosis higher than grade B were defined as significant risk factors. The highest odds ratio was obtained for F0 vs. F1-F3 (p = 0.038). DMPD (p < 0.001), pre-SI (p = 0.008), portal-SI/pre-SI (p < 0.001), transitional-SI/pre-SI (p < 0.001), and hepatobiliary-SI/pre-SI (p = 0.012) were significantly correlated with the presence of fibrosis. The presence of fibrosis was best detected by DMPD (AUC = 0.777). Individual specificity values of transitional-SI/pre-SI and DMPD were 95.5% and 86.6%, respectively, and their combined specificity was 97.7%.

Conclusion: The absence of pancreatic fibrosis is a risk factor for developing POPF higher than grade B. DMPD was the most useful diagnostic indicator of the presence of fibrosis among our analysis, and its specificity increased when combined with transitional-SI/pre-SI.
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http://dx.doi.org/10.2174/1573405617666210311114017DOI Listing
March 2021

Accumulation of cellular prion protein within β-amyloid oligomer plaques in aged human brains.

Brain Pathol 2021 Feb 23:e12941. Epub 2021 Feb 23.

Experimental Dementia Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.

Alzheimer's disease (AD) is the main cause of dementia, and β-amyloid (Aβ) is a central factor in the initiation and progression of the disease. Different forms of Aβ have been identified as monomers, oligomers, and amyloid fibrils. Many proteins have been implicated as putative receptors of respective forms of Aβ. Distinct forms of Aβ oligomers are considered to be neurotoxic species that trigger the pathophysiology of AD. It was reported that cellular prion protein (PrP ) is one of the most selective and high-affinity binding partners of Aβ oligomers. The interaction of Aβ oligomers with PrP is important to synaptic dysfunction and loss. The binding of Aβ oligomers to PrP has mostly been studied with synthetic peptides, cell culture, and murine models of AD by biochemical and biological methods. However, the molecular mechanisms underlying the relationship between Aβ oligomers and PrP remain unclear, especially in the human brain. We immunohistochemically investigated the relationship between Aβ oligomers and PrP in human brain tissue with and without amyloid pathology. We histologically demonstrate that PrP accumulates with aging in human brain tissue even prior to AD mainly within diffuse-type amyloid plaques, which are composed of more soluble Aβ oligomers without stacked β-sheet fibril structures. Our results suggest that PrP accumulating plaques are associated with more soluble Aβ oligomers, and appear even prior to AD. The investigation of PrP accumulating plaques may provide new insights into AD.
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http://dx.doi.org/10.1111/bpa.12941DOI Listing
February 2021

Ruptured mediastinal mature teratoma causing severe mediastinitis: report of a surgically resected case and a literature review.

Surg Case Rep 2021 Feb 16;7(1):48. Epub 2021 Feb 16.

Department of Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Background: Mediastinal teratomas occasionally rupture into the thoracic cavity, which induces mediastinitis or various other severe complications. Surgical treatment is crucial for ruptured teratomas; however, few literature reviews to date have addressed the characteristics of ruptured mediastinal teratomas.

Case Presentation: We report a 29-year-old woman with severe mediastinitis owing to a mediastinal mature teratoma that ruptured into the mediastinum and right pleural cavity. Surgical resection by median sternotomy was performed within 24 hours after emergency admission. Intraoperative findings demonstrated the ruptured wall of the tumor with exposure of its white contents, which appeared similar to skin and fat, and necrotic tissue in the anterior mediastinum. The tumor was adhered to the right upper lobe, the ascending aorta, and pericardium. Owing to the severe adhesion of the tumor caused by inflammation in the surrounding tissues, a small portion of the tumor could not be removed, and hence complete resection with a sufficient surgical margin was not achieved. Pathologically, the tumor consisted of a solid mass and a cystic mass with severe adhesion to the resected portion of the lung, which included skin and lipid tissue. The tumor was concluded to be a mature teratoma as neither an immature component nor malignant transformation was observed. The patient had an uneventful postoperative course.

Conclusions: To our knowledge, this is the report of successful surgical resection of a ruptured mediastinal teratoma causing severe mediastinitis, with the first literature review of ruptured mediastinal teratomas. We also discuss relevant findings from reports in the literature.
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http://dx.doi.org/10.1186/s40792-021-01132-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886921PMC
February 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 Jan 19. Epub 2021 Jan 19.

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA Department of Pathology and Laboratory Medicine, Nagoya University Graduate School of Medicine, Nagoya Departments of Anatomic Pathology Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo Department of Diagnostic Pathology, Fujita Health University, School of Medicine, Toyoake, Japan.

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
January 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

Diffusion-weighted imaging might be useful for reactive lymphoid hyperplasia diagnosis of the liver: A case report.

World J Clin Cases 2020 Nov;8(21):5313-5319

Department of Anatomic Pathology, Tokyo Medical University, Tokyo 1600023, Japan.

Background: Reactive lymphoid hyperplasia (RLH) of the liver is a rare liver lesion. It is considered difficult to differentiate radiologically from hepatocellular carcinoma, metastatic liver tumor and other pathologies.

Case Summary: A 54-year-old woman presented to our hospital with RLH of the liver. The patient had a diagnosis of metastatic carcinoma of the liver from an unknown origin and subsequently underwent partial hepatectomy. However, histopathological analysis revealed RLH. The lesion showed perinodular enhancement in the arterial phase on contrast-enhanced computed tomography and magnetic resonance imaging. On diffusion-weighted imaging (DWI), we encountered linear hyperintensity along the portal tract consecutive to the liver lesion, which is a new characteristic radiologic finding. This finding corresponded to the lymphoid cell infiltration of the portal tract. Furthermore, there was strongly restricted diffusion on the apparent diffusion coefficient map. We used these characteristic radiologic findings to diagnose the lesion as a lymphoproliferative disease.

Conclusion: The linear hyperintensity consecutive to the liver lesion on DWI provided additional valuable diagnostic information.
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http://dx.doi.org/10.12998/wjcc.v8.i21.5313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674723PMC
November 2020

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

Multicentre, retrospective study of the efficacy and safety of nivolumab for recurrent and metastatic salivary gland carcinoma.

Sci Rep 2020 10 12;10(1):16988. Epub 2020 Oct 12.

Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, Tokyo, 108-8329, Japan.

Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab's efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.
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http://dx.doi.org/10.1038/s41598-020-73965-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552420PMC
October 2020

A Rare Case of Ectopic Adrenocorticotropic Hormone Syndrome with Recurrent Olfactory Neuroblastoma.

Intern Med 2021 Jan 12;60(1):105-109. Epub 2020 Sep 12.

Department of Diabetes, Metabolism, Endocrinology, Rheumatology and Collagen Diseases, Tokyo Medical University, Japan.

A 40-year-old woman who had a history of recurrent olfactory neuroblastoma presented with full moon face, central obesity, buffalo hump, impaired glucose tolerance and bilateral cervical lymph node swelling. Laboratory tests showed morbidly elevated levels of adrenocorticotropic hormone (ACTH) and cortisol, which were not suppressed by high-dose (8 mg) dexamethasone. Biopsies of the enlarged cervical lymph nodes revealed ACTH-positive metastatic olfactory neuroblastoma, and ectopic ACTH syndrome was diagnosed. Metyrapone was used to suppress cortisol production and resulted in decreased levels of ACTH and cortisol. Bilateral cervical tumor resection further reduced the ACTH and cortisol levels, accompanied by a reduction in the metyrapone dosage. Cushing's syndrome was alleviated through ACTH-producing tumor removal.
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http://dx.doi.org/10.2169/internalmedicine.2897-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835471PMC
January 2021

Prognostic impact of CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study.

Cancer Sci 2020 Nov 14;111(11):4195-4204. Epub 2020 Sep 14.

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

Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3-MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3-MAML2 fusions were detected using FISH and RT-PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3-MAML2 fusions. During the follow-up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion-positive patients died during the follow-up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced-stage MEC cohorts, but not in the early-stage MEC cohort. In conclusion, CRTC1/3-MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC.
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http://dx.doi.org/10.1111/cas.14632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648036PMC
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

Painful proctitis with mixed infection due to herpes simplex virus types 1 and 2 and Chlamydia trachomatis.

Int J Infect Dis 2020 09 6;98:406-407. Epub 2020 Jul 6.

Department of Infection Prevention and Control, Tokyo Medical University Hospital, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.ijid.2020.07.002DOI Listing
September 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

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

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and Japanese Society of Clinical Cytology: An Interobserver Reproducibility Study and Risk of Malignancy Evaluation on Cytology Specimens.

Acta Cytol 2020 27;64(5):452-462. Epub 2020 Mar 27.

Department of Thoracic Surgery, Kitasato University School of Medicine, Sagamihara, Japan.

Introduction: The classification of lung carcinoma is based on small biopsies and/or cytology in 80% of patients with non-small cell carcinoma. However, there is no widely accepted classification system for respiratory cytology. The Japan Lung Cancer Society (JLCS) and Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma with the following categories: (1) "negative for malignancy," (2) "atypical cells," (3) "suspicious for malignancy," and (4) "malignancy."

Objective: The aim of this work was to perform an interobserver reproducibility study to confirm the utility of the four-tiered reporting system on respiratory cytological samples.

Methods: We analyzed 90 cytological samples obtained with bronchoscopy. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the three-, four-, and five-tiered reporting systems.

Results: The interobserver agreement was fair in the three- (κ = 0.50), four- (κ = 0.45), and five-tiered (κ = 0.45) reporting systems. However, the four-tiered reporting system provided more precise information than the three-tiered reporting system in patient management. The risk of malignancy in the four-tiered reporting system was also stratified well: 19.3% for "negative for malignancy," 45.6% for "atypical cells," 74.7% for "suspicious for malignancy," and 88.1% for "malignancy."

Conclusions: The reporting system proposed by the JLCS and JSCC was designed to enhance the communication between clinicians and pathologists and among different institutions. It is simple and applicable to cytological diagnosis of any respiratory diseases. We propose establishing an international classification for respiratory cytology, harmonizing the reporting systems proposed by different countries.
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http://dx.doi.org/10.1159/000506431DOI Listing
September 2020

Neck dissection prolongs survival in patient with stage IVC hypopharyngeal carcinoma with mixed responses to nivolumab.

Auris Nasus Larynx 2021 Apr 12;48(2):322-326. Epub 2020 Mar 12.

Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Tokyo, Japan.

Surgical intervention aids in maintaining quality of life in patients with recurrent metastatic head and neck carcinoma with mixed responses to nivolumab treatment. However, the mechanisms involved in these mixed responses remain unclear. Systemic chemotherapy using the EXTREME regimen was administered to the patient with hypopharyngeal carcinoma and liver metastases as well as cervical lymph node metastases. The patient was subsequently treated with nivolumab after developing signs of progressive disease. Although the hypopharyngeal tumors and liver metastases were well-controlled, cervical lymph node dissection was performed because of the enlargement of some of the lymph node metastases. Postoperative nivolumab administration was resumed, and this patient is presently alive and disease-free. Immediately after neck dissection, the LNs that responded and those that did not respond to nivolumab were separated and evaluated. The LNs that responded well to nivolumab presented with prominent interstitial fibrosis. Conversely, in LNs that enlarged after nivolumab, significant proliferation of the viable tumor cells and almost no degeneration or necrosis was observed. Additionally, we performed immunohistological assessments on pathologic samples of multiple lesions with differing responses to treatment. Targeted surgical intervention appears to be a valuable adjunct to treatment with nivolumab.
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http://dx.doi.org/10.1016/j.anl.2020.02.014DOI Listing
April 2021

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

Salvage carbon ion radiotherapy for recurrent solitary fibrous tumor: A case report and literature review.

J Orthop Surg (Hong Kong) 2020 Jan-Apr;28(1):2309499019896099

Division of Radiation Oncology, QST Hospital, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

Background: Malignant solitary fibrous tumor (MSFT) arising from the spinal cord is extremely rare and poorly understood mesenchymal neoplasms: only a few MSFT in the spinal canal has been described. We describe the clinical course of the patient with MSFT arising from the thoracic spinal cord.

Case Report: We describe the clinical course of the patient and the radiological and pathological findings of the tumor. The tumor had been resected by microscopic posterior approach and video-assisted thoracic surgery, but local recurrence was observed by MRI at 1-year follow-up period. No metastatic lesion was confirmed. Then, carbon ion radiotherapy (CIRT) was administered to the recurrent lesion. Local suppression has been observed for 40 months after irradiation.

Conclusion: Dumbbell-shaped MSFT arising from thoracic spinal cord is a highly unusual presentation. CIRT might be effective for treatment of recurrent tumors.
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http://dx.doi.org/10.1177/2309499019896099DOI Listing
December 2020

Giant cell arteritis in a patient with aortic dissection: a case report.

Cardiovasc Pathol 2020 May - Jun;46:107206. Epub 2020 Jan 23.

Department of Pathology and Biobank, National Cerebral and Cardiovascular Center, 6-1 Kishibe-shinmachi, Suita, 564-8565, Japan.

Aortic lesions, such as an aortic aneurysm, are known as a late complication that usually occurs several years after the onset of giant cell arteritis. Here, we report a rare case of large-vessel giant cell arteritis in a patient with aortic dissection. A 71-year-old man presented with acute back pain and was diagnosed with aortic dissection, Stanford type A, and he underwent elective ascending aortic replacement. Further studies showed that the resected ascending aorta had aortic dissection and multinucleated giant cell granulomas; the granulomas were located in the media near the intima with partial destruction of the internal elastic lamina; there was no stenosis of the feeding blood vessel or fibrosis of the adventitia as observed in Takayasu arteritis; other types of vasculitis were considered unlikely based on the symptoms and laboratory data. The patient was further diagnosed with giant cell arteritis, which was classified as a large vessel vasculitis along with Takayasu arteritis at the Chapel Hill Consensus Conference in 2012. This is a rare case of giant cell arteritis diagnosed in a patient with aortic dissection. The differences in histopathological findings between Takayasu arteritis and giant cell arteritis are discussed.
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http://dx.doi.org/10.1016/j.carpath.2020.107206DOI Listing
June 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

Clinical and pathological predictors of recurrence in breast cancer patients achieving pathological complete response to neoadjuvant chemotherapy.

Eur J Surg Oncol 2019 Dec 2;45(12):2289-2294. Epub 2019 Aug 2.

Department of Breast Oncology and Surgery, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan. Electronic address:

Introduction: Despite the excellent prognosis associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), some patients still develop recurrence. Here, we investigated the outcomes of breast cancer patients with pCR, as well as the clinical and pathological predictors of cancer recurrence in these patients.

Materials And Methods: Of the 1599 breast cancer patients treated with NAC, we evaluated 394 patients who achieved pCR between January 2007 and December 2016. pCR was defined as no evidence of invasive cancer in breast. Residual in situ ductal and axillary lymph node diseases were not considered. We analyzed the outcomes using the Kaplan-Meier method. We assessed the association of clinical and pathological predictors with cancer recurrence using the cox proportional hazards regression model.

Results: The median follow-up time was 63 months. The 5-year disease-free survival rate was 92.3%. Cancer recurrence was observed in 28 patients (7.1%): local recurrence 8 patients (2.0%), visceral metastasis 10 patients (2.5%), and brain metastasis 10 patients (2.5%). Brain metastases were found in patients with HER2 type breast cancer. The significant predictors of cancer recurrence were HER2 positivity (p = 0.04), clinical tumor size (p < 0.01), and lymph node metastasis (p < 0.01) before NAC on univariate analysis and only lymph node metastasis on multivariate analysis.

Conclusion: Patients achieving pCR to NAC showed excellent outcomes. Advanced clinical stage, large tumor size, presence of lymph node metastasis, and HER2 positivity before NAC were identified as significant predictors of cancer recurrence. Residual in situ ductal and lymph node diseases after NAC were not significant predictors.
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http://dx.doi.org/10.1016/j.ejso.2019.08.001DOI Listing
December 2019

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

A case of primary clear cell hepatocellular carcinoma comprised mostly of clear cells.

Radiol Case Rep 2019 Nov 16;14(11):1377-1381. Epub 2019 Sep 16.

Department of Anatomic Pathology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.

Clear cell hepatocellular carcinoma (CHCC) is defined as a tumor which contains more than 50% of clear cells. However, CHCC with more than 90% of clear cells are extremely rare. We report a case of a 65-year-old woman who was found to have a solitary mass, which was histologically diagnosed as clear cell hepatocellular carcinoma composed of 90% or more clear cells. The tumor presented rim arterial phase hyperenhancement in computed tomography, magnetic resonance imaging, and computed tomography during hepatic arteriography, and was classified as LR-M category according to The Liver Imaging Reporting and Data System version 2018(LI-RADS v2018). This tumor may mimic other tumors with similar radiographic features, such as intrahepatic cholangiocellular carcinoma and metastatic tumor.
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http://dx.doi.org/10.1016/j.radcr.2019.08.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823767PMC
November 2019