Publications by authors named "Ryuji Ohashi"

86 Publications

Solitary chondrosarcoma of the right ring finger: A case report.

J Nippon Med Sch 2021 Sep 14. Epub 2021 Sep 14.

Department of Orthopaedic Surgery, Nippon Medical School.

We present a case of solitary chondrosarcoma arising from the proximal phalanx of the ring finger in an elderly man. The chondrosarcoma developed over a period of 14 years, during which the phalanx became progressively more deformed. Several radiographic investigations were carried out, but the patient declined further suggested diagnostic examinations (computed tomography, magnetic resonance imaging, biopsy). Eventually, the lesion became significantly enlarged, and radiographs showed osteolytic lesions in the phalangeal bone. Ray amputation of the finger was required to establish a wide resection of the chondrosarcoma. Most osteochondral tumors arising from the phalanges are benign tumors such as enchondromas, but primary chondrogenic malignant bone tumors (chondrosarcomas) occasionally occur. Chondrosarcoma of the phalanx is difficult to distinguish from enchondroma of the phalanx, because histological investigations of the two neoplasms often produce similar findings. Even with a combination of clinical, biopsy, and imaging findings, differentiating these neoplasms is still challenging, because the characteristic clinical and radiological features of chondrosarcoma do not appear until it becomes aggressive and starts to cause destructive changes. Once that happens, radical expanded resection of the tumor is essential. Therefore, longstanding enchondroma-like lesions should be actively treated in elderly patients, even if a definite diagnosis of chondrosarcoma cannot be made.
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http://dx.doi.org/10.1272/jnms.JNMS.2022_89-602DOI Listing
September 2021

A rapidly growing small intestinal metastasis from lung cancer.

J Nippon Med Sch 2021 Sep 14. Epub 2021 Sep 14.

Department of Pathology, Nippon Medical School.

Small intestinal metastasis from lung cancer is a relatively rare occurrence, and often causes intestinal obstruction, gastrointestinal perforation, and/or gastrointestinal bleeding making it is an oncological emergency. Many patients have been reported to undergo emergency surgery owing to the rapid progression of the intestinal metastatic lesion; however, information regarding the changes that occur in such metastases over time remains lacking. Therefore, we analyzed 4 patients who had small intestinal metastases arising from lung cancer, who were treated during a 10-year period (January 2011 to December 2020), and whose tumor diameter changes were recorded. The average tumor volume growth rate was 1.48 (1.31-1.78) -fold, and the median observation period was 22 (4-39) days, showing a rapid increase. Histopathologically, in patients with a high degree of primary tumor atypia, rapid tumor growth caused by intratumoral hemorrhage may occur. This was considered to be one of the factors responsible for the rapid increase in tumor volume.
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http://dx.doi.org/10.1272/jnms.JNMS.2022_89-501DOI Listing
September 2021

An advanced case of gastric histiocytic sarcoma treated with chemotherapy and gastrectomy: a case report and review of literature.

Clin J Gastroenterol 2021 Aug 8;14(4):1053-1059. Epub 2021 Jun 8.

Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Histiocytic sarcoma is a relatively new disease category and the gastrointestinal origin is sporadic. We report a case of a 74-year-old woman who underwent chemotherapy and proximal gastrectomy for extremely rare, advanced gastric histiocytic sarcoma. The resected specimen was subjected to numerous immunostainings to meet the diagnostic criteria of histiocytic sarcoma and was positive for the histiocyte markers' cluster of differentiation 68 and lysozyme. The markers of Langerhans cells, follicular dendritic cells, and myelocyte were all negative. Six reports of surgical resection of histiocytic sarcoma originating in the stomach exist, including our case. We reviewed the clinical course and the histological and immunohistochemical diagnostic features of surgically resected gastric histiocytic sarcoma.
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http://dx.doi.org/10.1007/s12328-021-01438-yDOI Listing
August 2021

Renal Involvement as Rare Acute Tubulointerstitial Nephritis in a Patient with Eosinophilic Disorder Treated with Early Add-on Administration of Mepolizumab.

Intern Med 2021 Jun 5. Epub 2021 Jun 5.

Department of Internal Medicine, Teikyo University School of Medicine, Japan.

A 39-year-old man presented with peripheral eosinophilia, pulmonary eosinophilic infiltrate, and renal failure due to acute tubulointerstitial nephritis (TIN). He had experienced childhood asthma and was negative for anti-neutrophil cytoplasmic antibody (ANCA). He was tentatively diagnosed with ANCA-negative eosinophilic granulomatous polyangiitis (EGPA) or idiopathic hypereosinophilic syndrome (HES). Renal involvement of isolated TIN with eosinophil infiltration is rare in EGPA and HES and does not seem to have a good prognosis in the literature. However, his condition improved well with corticosteroids and mepolizumab. The revised classification of EGPA based on the etiology should dictate the proper treatment in suspected EGPA patients with nonsystemic vasculitis.
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http://dx.doi.org/10.2169/internalmedicine.7490-21DOI Listing
June 2021

Early Transplant Arteriopathy in Kidney Transplantation.

Transplant Proc 2021 Jun 4;53(5):1554-1561. Epub 2021 May 4.

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington. Electronic address:

Background: Early dysfunction of renal allografts may be associated with vascular injury, which raises the specter of active rejection processes that require medical intervention. In our practice, we have encountered patients who present with delayed graft function and demonstrate a unique pattern of endothelial cell injury that raises concern for rejection in their biopsy. Therefore, we sought to systematically determine the biopsy characteristics and outcome of these patients.

Methods: During a 17-year period at the University of Washington in Seattle, United States, we identified 24 cases of a distinct arterial vasculopathy presenting in the first year posttransplantation. This early transplant arteriopathy (ETA) is characterized by endothelial cell swelling and intimal edema but without the intimal arteritis that defines vascular rejection.

Results: Approximately 1% of transplant biopsies during the study period showed ETA, almost all of which were in deceased donor organs (96%), and most presented with delayed graft function (54%) or increased serum creatinine (38%) soon after transplantation (median 13 days; range, 5-139). In this study, 77% of patients were managed expectantly, with only 2 patients (7.6%) subsequently developing acute vascular rejection. Except for 1 patient who died, all patients had functioning allografts at 1 year follow-up.

Conclusion: Recognizing ETA and distinguishing it from vascular rejection is important to prevent over-treatment because most patients appear to recover allograft function rapidly with expectant management.
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http://dx.doi.org/10.1016/j.transproceed.2021.02.019DOI Listing
June 2021

Clinical Utility of Fine Needle Aspiration Cytology for Adenoid Cystic Carcinoma of the Trachea with Thyroid Invasion: A Case Report.

J Nippon Med Sch 2021 Apr 19. Epub 2021 Apr 19.

Department of Endocrine Surgery, Nippon Medical School.

Background: Adenoid cystic carcinoma of the trachea (ACCT) is a rare cancer; ACCT with thyroid invasion is particularly rare. We first suspected anaplastic thyroid carcinoma (ATC) but diagnosed ACC after performing fine needle aspiration cytology (FNAC). A tracheal origin was confirmed after operation.

Case Description: We report the case of a 77-year-old female presenting to our hospital with acute inspiratory dyspnea requiring emergency tracheotomy. Physical examination revealed a right anterior neck swelling with a hard and unmovable mass. Computed tomography (CT) and ultrasonography (US) showed tumor extension to the right thyroid lobe, and between the first and third tracheal rings, which caused severe stenosis of the lumen. Next, we performed FNAC. Clinical findings were highly suspicious for ACCT with thyroid invasion. Thirty-five days after the first visit to our department, the patient underwent total laryngectomy, cervical esophagectomy, and thyroidectomy with bilateral selective neck dissections at another hospital. The tumor was located in the right posterior wall of the trachea, with extension into the right thyroid gland. Pathological examination showed an infiltrative carcinomatous proliferation with tubular and cribriform patterns. The tumor was classified as pT4N1. A definite diagnosis was made after histopathological analyis of the surgical specimen confirmed ACCT. The tumor was found to be positive for FABP7, a putative prognostic marker of ACC, and metastasized to the lungs 3 years after the surgery.

Conclusions: ACCT with thyroid invasion is an extremely rare malignant neoplasm. FNAC was useful for differentiating ACCT from other diagnoses and enabled appropriate surgical treatment.
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http://dx.doi.org/10.1272/jnms.JNMS.2022_89-207DOI Listing
April 2021

PIK3CA mutation detected by liquid biopsy in patients with metastatic breast cancer.

J Nippon Med Sch 2021 Mar 9. Epub 2021 Mar 9.

Department of Breast Surgery and Oncology, Nippon Medical School.

Background: PIK3CA is associated with tumor progression, and the prevalence of its mutation is high in breast cancer. Liquid biopsy offers convenient, non-invasive, and real-time insight into genetic alternation. In this study, we attempted to detect PIK3CA mutations in breast cancer patients through liquid biopsy.

Methods: We recruited patients with histologically confirmed breast cancer with distant metastases between April 2020 and September 2020. Circulating DNA was extracted from plasma (ctDNA) and exosomes (exoDNA). PIK3CA mutations (exons 9 and 20) were analyzed by droplet digital PCR.

Results: Of a total of 52 patients recruited, 16 had PIK3CA mutations in their tumor tissue or blood, which comprised 9 with exon 9 mutations (E542K and E545K) and 8 with exon 20 mutations (H1047L and H1047R). In 8 (15%) of the 52 patients, PIK3CA mutations were detected by liquid biopsies using ctDNA in 5 (9%), exoDNA in 6 (11%), and both ctDNA and exoDNA in 3 (6%). Of the 8 patients with PIK3CA mutations detected by liquid biopsies, 3 had no PIK3CA mutations in the primary tumors.

Conclusions: PIK3CA mutations can be detected using liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.
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http://dx.doi.org/10.1272/jnms.JNMS.2022_89-107DOI Listing
March 2021

Neoadjuvant endocrine therapy in women with operable breast cancer: A retrospective analysis of real-world use.

J Nippon Med Sch 2021 Mar 9. Epub 2021 Mar 9.

Department of Integrated Diagnostic Pathology, Nippon Medical School.

Background: A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing its role in breast cancer care.

Materials And Methods: In a consecutive series of women with operable breast cancer who received NET for ≥28 days, NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survivals, were examined for the correlation with clinicopathological factors.

Results: NET objectives were for surgery extent reduction in 49 patients, surgery avoidance in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1923), 869.8 (range, 36-4859), and 55.8 (range, 39-113) days in the above cohorts (success: 79.6%, 64.5%, and 100%), respectively, with significant difference. In patients of the former two cohorts, better progression-free survival was significantly correlated with stage 0 or I, ductal carcinoma in situ or invasive ductal carcinoma, ≥71% estrogen receptor (ER) positivity, and the surgery extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly correlated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high Preoperative Endocrine Prognostic Index, at surgery after NET. Better recurrence-free survival after surgery was significantly correlated with high ER expression after NET and high PgR expression before and after NET.

Conclusions: NET can help to reduce the surgery extent or to avoid surgery in women with breast cancer of early-stage, ductal carcinoma, or high ER expression. NET may also contribute to appropriate decision of postoperative systemic therapy to improve survivals.
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http://dx.doi.org/10.1272/jnms.JNMS.2021_88-603DOI Listing
March 2021

Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up.

J Clin Biochem Nutr 2021 Jan 17;68(1):86-94. Epub 2020 Sep 17.

Department of Gastroenterology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.
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http://dx.doi.org/10.3164/jcbn.19-130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844654PMC
January 2021

Membranous nephropathy with thrombotic microangiopathy-like lesions successfully treated with tocilizumab in a patient with idiopathic multicentric Castleman disease.

CEN Case Rep 2021 05 2;10(2):265-272. Epub 2021 Jan 2.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, Japan.

Idiopathic multicentric Castleman disease (iMCD) is a systemic lymphoproliferative disease involving multiple organs, including the kidneys. Membranous nephropathy (MN) has been rarely reported as a complication of iMCD. We herein report the case of a 48-year-old man with a 9-year history of iMCD that was complicated by treatment-resistant nephrotic syndrome due to MN. The first renal biopsy performed at the age of 45 years showed diffuse and global MN with a mild glomerular endothelial injury. He was treated with combined therapy of corticosteroids, immunosuppressants, and tocilizumab, an anti-interleukin-6 (IL-6) receptor monoclonal antibody, which was administered every 2-3 weeks. However, nephrotic syndrome persisted, and renal impairment slowly worsened. Serial biopsy performed at 3 years after the first biopsy confirmed advanced lesions of both MN-related and glomerular endothelial injuries. Modification of the therapeutic strategy to weekly administration of tocilizumab gradually led to the remission of proteinuria, allowing the termination of corticosteroids. Thus, the present case suggests a close link between excessive IL-6 actions and the development of glomerular lesions in iMCD. Successful treatment by strict inhibition of IL-6 actions, in this case, may provide a clue for deciding the therapeutic strategy for severe renal complications associated with iMCD.
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http://dx.doi.org/10.1007/s13730-020-00559-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019444PMC
May 2021

Thyroid Hürthle Cell Carcinoma: Clinical, Pathological, and Molecular Features.

Cancers (Basel) 2020 Dec 23;13(1). Epub 2020 Dec 23.

Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyoku, Tokyo 113-8602, Japan.

Hürthle cell carcinoma (HCC) represents 3-4% of thyroid carcinoma cases. It is considered to be more aggressive than non-oncocytic thyroid carcinomas. However, due to its rarity, the pathological characteristics and biological behavior of HCC remain to be elucidated. The Hürthle cell is characterized cytologically as a large cell with abundant eosinophilic, granular cytoplasm, and a large hyperchromatic nucleus with a prominent nucleolus. Cytoplasmic granularity is due to the presence of numerous mitochondria. These mitochondria display packed stacking cristae and are arranged in the center. HCC is more often observed in females in their 50-60s. Preoperative diagnosis is challenging, but indicators of malignancy are male, older age, tumor size > 4 cm, a solid nodule with an irregular border, or the presence of psammoma calcifications according to ultrasound. Thyroid lobectomy alone is sufficient treatment for small, unifocal, intrathyroidal carcinomas, or clinically detectable cervical nodal metastases, but total thyroidectomy is recommended for tumors larger than 4 cm. The effectiveness of radioactive iodine is still debated. Molecular changes involve cellular signaling pathways and mitochondria-related DNA. Current knowledge of Hürthle cell carcinoma, including clinical, pathological, and molecular features, with the aim of improving clinical management, is reviewed.
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http://dx.doi.org/10.3390/cancers13010026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793513PMC
December 2020

Inhibitor for protein disulfide-isomerase family A member 3 enhances the antiproliferative effect of inhibitor for mechanistic target of rapamycin in liver cancer: An study on combination treatment with everolimus and 16F16.

Oncol Lett 2021 Jan 11;21(1):28. Epub 2020 Nov 11.

Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan.

mTOR is involved in the proliferation of liver cancer. However, the clinical benefit of treatment with mTOR inhibitors for liver cancer is controversial. Protein disulfide isomerase A member 3 (PDIA3) is a chaperone protein, and it supports the assembly of mTOR complex 1 (mTORC1) and stabilizes signaling. Inhibition of PDIA3 function by a small molecule known as 16F16 may destabilize mTORC1 and enhance the effect of the mTOR inhibitor everolimus (Ev). The aim of the present study was to elucidate the usefulness of combination treatment with Ev and 16F16 in liver cancer using cultured Li-7 and HuH-6 cells. The proliferation of cultured cells was examined following treatment with 0.01 µM Ev, 2 µM 16F16 or both. The expression levels and phosphorylation of S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1) were examined by western blotting. Li-7 was susceptible to Ev, and proliferation was reduced to 69.5±7.2% by Ev compared with that of untreated cells. Proliferation was reduced to 90.2±10.8% by 16F16 but to 62.3±12.2% by combination treatment with Ev and 16F16. HuH-6 cells were resistant to Ev, and proliferation was reduced to 86.7±6.1% by Ev and 86.6±4.8% by 16F16. However, combination treatment suppressed proliferation to 57.7±4.0%. Phosphorylation of S6K was reduced by Ev in both Li-7 and HuH-6 cells. Phosphorylation of 4E-BP1 was reduced by combination treatment in both Li-7 and HuH-6 cells. Immunoprecipitation assays demonstrated that PDIA3 formed a complex with 4E-BP1 but not with S6K. The small molecule 16F16 increased susceptibility to Ev in cultured liver cancer cells, which are resistant to Ev. The inhibition was associated with reduction of 4E-BP1 phosphorylation, which formed a complex with PDIA3. Combination treatment with Ev and 16F16 could be a novel therapeutic strategy for liver cancer.
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http://dx.doi.org/10.3892/ol.2020.12289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681208PMC
January 2021

Multicentric endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma of the skin: A case report.

J Cutan Pathol 2021 Jan 8;48(1):165-170. Epub 2020 Nov 8.

Department of Dermatology, Nippon Medical School Musashi Kosugi Hospital, Kawasaki, Kanagawa, Japan.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade sweat gland carcinoma. EMPSGC is thought to be a precursor to mucinous carcinoma of the skin (MCS). Since the first description of EMPSGC in 1997, only a few cases have been reported, and its etiology and mechanisms remain unknown. In this report, we describe a 71-year-old Japanese woman with two isolated EMPSGC and one MCS lesion on her face. She was simultaneously diagnosed with invasive ductal carcinoma of the breast. She had a history of uterine cancer of unknown histopathological diagnosis 24 years previously. The presence of in situ lesions confirmed by myoepithelial cells suggested that the cutaneous lesions were primary tumors. To the best of our knowledge, this is the first case of multiple primary EMPSGC/MCS tumors. Additionally, this might be the first case with multiple primary carcinomas including adnexal cutaneous tumors, breast cancer, and uterine cancer, which may share the common feature of expressing female hormonal receptors. This case indicates that EMPSGC/MCS may be triggered by a hormonal receptor abnormality, perhaps because of genetic defects. A larger number of reports examining this issue may be necessary to further assess our initial observations.
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http://dx.doi.org/10.1111/cup.13896DOI Listing
January 2021

High Expression of p21 as a Potential Therapeutic Target in Ovarian Clear-cell Carcinoma.

Anticancer Res 2020 Oct;40(10):5631-5639

Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan.

Background/aim: DNA damage response (DDR), wherein p21 is a cell fate determinant, is a potential cancer therapeutic target. Molecular expression during DDR was explored in ovarian clear-cell carcinoma (CCC).

Materials And Methods: CHK1, CHK2, TP53 and p21 expression in DDR was examined using immunostaining in surgical sections of CCC (n=22). Molecular alterations in two types of CCC cell lines, JHOC-5 and JHOC-9, were investigated using western blot analysis.

Results: Expression of DDR-associated molecules was noted in most patients. While high p21 expression was found in half of the patients, the remaining patients exhibited low p21 expression. Treatment with UC2288, a p21 inhibitor, attenuated proliferation of both cell lines, more prominently in JHOC-9, resulting in reduced viability and subsequent apoptosis.

Conclusion: p21 Inhibitor induced cell death in cells with high p21 expression, suggesting that p21 suppression can be a therapeutic strategy to treat patients with CCC.
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http://dx.doi.org/10.21873/anticanres.14576DOI Listing
October 2020

Pyuria without Casts and Bilateral Kidney Enlargement Are Probable Hallmarks of Severe Acute Kidney Injury Induced by Acute Pyelonephritis: A Case Report and Literature Review.

Intern Med 2021 Jan 5;60(2):293-298. Epub 2020 Sep 5.

Department of Internal Medicine, Teikyo University School of Medicine, Japan.

The patient was a 38-year-old man who had experienced nausea and fever for a few days and presented with back pain, oliguria, and pyuria, suggesting acute pyelonephritis (APN). He showed acute kidney injury (AKI) with bilateral kidney enlargement and was using nonsteroidal anti-inflammatory drugs (NSAIDs). AKI-induced by APN was confirmed by kidney biopsy. The AKI was successfully treated with antibiotic therapy. A search of the relevant literature for reports on histopathologically-proven APN-induced severe AKI revealed that the key characteristics were bilateral kidney enlargement with pyuria without casts. Oligoanuria was frequently associated with APN-induced severe AKI, and NSAID use may be a possible risk factor. Prompt antibiotic treatment based on the clinical characteristics of APN-induced AKI can improve the renal outcome.
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http://dx.doi.org/10.2169/internalmedicine.5721-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872795PMC
January 2021

Utility of duct-washing cytology for detection of early breast cancer in patients with pathological nipple discharge: A comparative study with fine-needle aspiration cytology.

Diagn Cytopathol 2020 Dec 7;48(12):1273-1281. Epub 2020 Aug 7.

Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan.

Background: Pathological nipple discharge (PND) is a relatively common symptom of breast cancer affecting the nipple. Mammary ductscopy (MD) allows direct visualization of the ductal lumen and collection of a cytological specimen using duct-washing cytology (DWC). Herein, we clarified the diagnostic efficacy of DWC for the detection of breast cancers with PND, compared with fine-needle aspiration cytology (FNAC).

Methods: We retrospectively examined 48 patients with PND who underwent DWC by MD (ductosccopy group; histologically determined by intraductal biopsy [IDB] or surgical specimen). The results of sensitivity and specificity of DWC were compared with that of FNAC (conventional group; histologically determined by core needle biopsy). Clinicopathological factors were compared between the ductoscopy and the conventional groups.

Results: Of eight histologically malignant cases in the ductoscopy group, one case was cytologically judged as malignant and three as indeterminate. Sensitivity and specificity of DWC were 50.0% and 82.5%, respectively. Malignant cases were mostly solid papillary carcinomas (SPCs), and benign cases were intraductal papillomas (IDPs). In the conventional group, sensitivity and specificity of FNAC were 88.0% and 38.2%, respectively, and malignant cases were mainly invasive carcinomas of no special type. Tumors in the ductocsopy group had more favorable prognostic features than those in the conventional group.

Conclusion: DWC has limited diagnostic value due to the high incidence of SPC, whose cytological features are indistinguishable from IDP. As DWC alone may be unreliable, comprehensive examination with IDB and MD findings is recommended.
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http://dx.doi.org/10.1002/dc.24572DOI Listing
December 2020

Pulmonary metastasectomy for esophageal basaloid squamous cell carcinoma component at 66 months after esophagectomy.

Surg Case Rep 2020 Aug 5;6(1):199. Epub 2020 Aug 5.

Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.

Background: Solitary pulmonary metastasis from esophageal basaloid squamous cell carcinoma (BSCC) components is an extremely rare recurrence of esophageal squamous cell carcinoma (SCC).

Case Presentation: A 68-year-old Japanese woman was found to have a suspected malignant mass, approximately 2 cm in diameter, in her left lower pulmonary lobe, at 66 months after undergoing a curative esophagectomy with three-field lymph node dissection for esophageal SCC with a focal basaloid component. After a CT-guided biopsy, pathological examination indicated a metastasis from esophageal BSCC components. She underwent a thoracoscopic partial resection of the left lower pulmonary lobe for the solitary pulmonary metastasis. The pathohistology of the resected specimen led to diagnosis of metastatic esophageal BSCC, which showed immunohistochemical findings similar to those of the primary esophageal carcinoma. The patient received two courses of adjuvant chemotherapy (5-fluorouracil, docetaxel plus nedaplatin) and recovered to resume a normal life with maintenance therapy. However, multiple lung and brain metastases were diagnosed at 2 years after the pulmonary metastasectomy. She survived 5 years and 6 months after the pulmonary metastasectomy, but died at 10 years and 6 months after her initial esophagectomy.

Conclusion: This was a rare surgical resected case of solitary pulmonary metastasis from esophageal BSCC components.
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http://dx.doi.org/10.1186/s40792-020-00957-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406597PMC
August 2020

Sarcoid-like reaction in lymphadenopathy associated with superficial esophageal squamous cell carcinoma.

Clin J Gastroenterol 2020 Oct 9;13(5):688-692. Epub 2020 Jun 9.

Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.

Correctly distinguishing metastasis and sarcoid-like reaction in patients with mediastinal lymphadenopathy is clinically important in esophageal cancer. A patient was a 52-year-old Japanese woman with superficial esophageal squamous cell carcinoma and rare case of sarcoid-like reaction. The patient was admitted with pharyngeal discomfort and an upper gastrointestinal endoscopy detected a superficial tumor in the middle thoracic esophagus. Biopsy confirmed a diagnosis of squamous cell carcinoma. Chest computed tomography (CT) showed enlarged lymph nodes around the trachea and in the bilateral hilum of the lung that were found to accumulate label on positron emission tomography CT. One course of chemotherapy in 5-fluorouracil, docetaxel and cisplatin did not affect the lymphadenopathy, which suggested that it was reactive rather than metastatic. The patient had undergone thoracoscopic esophagectomy with lymph node dissection. The pathohistology of the dissected lymph nodes showed noncaseating epithelioid-cell granuloma and no malignant cells. No clinical findings indicative of systemic sarcoidosis were observed, leading to a diagnosis of sarcoid-like reaction with the esophageal cancer. The patient has survived without recurrence for 4 years after beginning the initial treatment. Monitoring the response to chemotherapy may be helpful in distinguishing between metastasis and sarcoidosis-associated lymphadenopathy in esophageal cancer.
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http://dx.doi.org/10.1007/s12328-020-01156-xDOI Listing
October 2020

Unique Clinical and Histological Features of Placental Mesenchymal Dysplasia Complicated by Severe Preeclampsia in the Midtrimester.

AJP Rep 2020 Jan 28;10(1):e113-e117. Epub 2020 Mar 28.

Department of Obstetrics and Gynecology, Nippon Medical School Hospital, Tokyo Japan.

Detailed clinical and pathological features of placental mesenchymal dysplasia (PMD) complicated by preeclampsia (PE) are unknown. A 39-year-old nulliparous woman was referred at 19 weeks gestation. Ultrasound examination identified a fetus with severe growth restriction (-2.8 SD) and a markedly thickened placenta with many cystic structures suggestive of PMD. At 21 weeks, the patient developed severe hypertension (180/95 mm Hg) with marked proteinuria and an elevated serum soluble fms-like tyrosine-kinase-1 (sFlt-1) level (47,000 pg/L). The pregnancy was terminated to protect maternal health. Placental weight was 450 g and no histopathological findings of either proliferation or dysplasia were observed in the trophoblast. Villous chromosome examination revealed a 46XX karyotype, consistent with the diagnosis of PMD. In addition to the pathological findings of vascular endothelial dysfunction characteristic of the placenta in PE cases, enhanced expression of sFlt-1 in the syncytiotrophoblast of the enlarged villi was confirmed by immunohistochemistry as a novel finding in this condition. Monitoring of the serum sFlt-1 value is suggested to be a useful predictor of the pathological change associated with extremely early severe PE in PMD cases.
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http://dx.doi.org/10.1055/s-0040-1709186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102899PMC
January 2020

Solid variant of papillary thyroid carcinoma: an under-recognized entity.

Authors:
Ryuji Ohashi

Endocr J 2020 Mar 25;67(3):241-248. Epub 2020 Jan 25.

Department of Diagnostic Pathology, Nippon Medical School Musashi-Kosugi Hospital, Kanagawa 211-8533, Japan.

Solid variant of papillary thyroid carcinoma (SVPTC) is a rare morphological variant of papillary thyroid carcinoma (PTC). SVPTC is histologically characterized by predominant solid, trabecular and insular nests of tumor cells while cytological features of PTC such as nuclear grooves and nuclear inclusions are preserved. In fine needle aspiration cytology smears, tumor cells of SVPTC may be presented in cohesive, syncytial or trabecular clusters accompanied by some discohesiveness in the absence of necrosis. Although SVPTC and poorly differentiated thyroid carcinoma (PDTC) share similar histological findings of solid nests, SVPTC can be differentiated from PDTC in the lack of tumor necrosis, severe nuclear atypia, and a higher mitotic index. Immunohistochemical expression of CK19 and HBME-1, common markers of PTC, is decreased in solid nests of SVPTC. In pediatric patients exposed to radiation after the Chernobyl nuclear accident, there was a higher prevalence of SVPTC with RET/PTC3 type rearrangement. BRAF mutations are also reported in a small number of adult patients with SVPTC without any prior radiation exposure. Patients with SVPTC may have a slightly higher incidence of metastasis and recurrence of the tumor compared to conventional PTC, although overall survival rate is comparable. In this article, the current knowledge of SVPTC will be reviewed and discussed with an emphasis on the histopathological feature.
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http://dx.doi.org/10.1507/endocrj.EJ19-0414DOI Listing
March 2020

Clinicopathological Implications of Proteinuria after Long-Term Isolated Hematuria due to Thin Basement Membrane Nephropathy and Focal Segmental Glomerulosclerosis.

Case Rep Nephrol 2019 17;2019:1627392. Epub 2019 Dec 17.

Department of Internal Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.

A 45-year-old obese man presented with persistent hematuria for 21 years. At the age of 37, he developed hypertension and proteinuria which later increased up to 1.6 g/g creatinine. Kidney biopsy revealed thin basement membrane nephropathy (TBMN) and focal segmental glomerulosclerosis (FSGS), which explained his urinary abnormalities. Although a subgroup of TBMN can be complicated by FSGS, his FSGS was associated with obesity because of its histological features. Reduction of body weight and increasing a dose of angiotensin-receptor blocker could transiently reduce the amount of proteinuria. Clinicopathological implications of proteinuria after long-term hematuria by TBMN and FSGS were further discussed.
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http://dx.doi.org/10.1155/2019/1627392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959157PMC
December 2019

Adipose tissue-derived stem cells suppress coronary arteritis of Kawasaki disease in vivo.

Pediatr Int 2020 Jan;62(1):14-21

Department of Pediatrics, Nippon Medical School, Sendagi, Tokyo, Japan.

Background: Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo.

Methods: Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared.

Results: The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1β, IL-12, IL-17, RANTES, INF-γ, and TNF-α, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group.

Conclusions: These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD.
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http://dx.doi.org/10.1111/ped.14062DOI Listing
January 2020

M1 macrophage is the predominant phenotype in coronary artery lesions following Kawasaki disease.

Vasc Med 2019 12 17;24(6):484-492. Epub 2019 Oct 17.

Department of Pediatrics, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.

Kawasaki disease (KD) is a systemic inflammatory process that affects the medium-sized arteries, causing various cardiovascular complications. However, it is not clear if the vascular sequelae following KD can predispose to the development of atherosclerosis later in life. Our aim was to examine the macrophage phenotypes in the coronary arteries forming giant aneurysms after KD to gain insight into the pathogenesis of vascular lesions in KD. We examined histological sections of the coronary arteries from five patients with KD who underwent coronary bypass grafting procedure as treatment for giant aneurysms and subsequent stenosis. Immunohistochemical expression of M1- and M2-macrophage markers was assessed to determine the macrophage phenotype of KD to compare with that of atherosclerosis in eight adult patients. All the KD specimens showed a mild to moderate degree of intimal thickening consisting of mature fibrous tissue and distortion of elastic fibers, mimicking the histological features of atherosclerosis. The total number of CD68 positive macrophages was higher in atherosclerosis than in KD specimens. Among the CD68 positive macrophages, the proportion of M1 phenotype, detected by CD86 or SOCS3, was higher in KD than in atherosclerosis. In contrast, the proportion of M2 phenotype, detected by CD163 or MRC1, was higher in patients with atherosclerosis. Despite similar histological features, KD and atherosclerosis appear to have a different immunological etiology for progression of the chronic vascular lesions. A further study enrolling a larger number of cases is required to delineate underlying mechanisms of vascular complications in KD.
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http://dx.doi.org/10.1177/1358863X19878495DOI Listing
December 2019

Editorial comment on the fate of full-house immunofluorescence staining in renal allograft: A case report.

Authors:
Ryuji Ohashi

Pathol Int 2019 11 18;69(11):661. Epub 2019 Sep 18.

Department of Diagnostic Pathology, Nippon Medical School Musashi-kosugi Hospital, Nakahara-ku, Japan.

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http://dx.doi.org/10.1111/pin.12848DOI Listing
November 2019

Possibility of Local Allergic Rhinitis in Japan.

Am J Rhinol Allergy 2020 Jan 14;34(1):26-34. Epub 2019 Aug 14.

Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.

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http://dx.doi.org/10.1177/1945892419868441DOI Listing
January 2020

Toll‑like receptor 4 plays a tumor‑suppressive role in cutaneous squamous cell carcinoma.

Int J Oncol 2019 Jun 17;54(6):2179-2188. Epub 2019 Apr 17.

Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113‑8603, Japan.

Toll‑like receptor 4 (TLR4), a key regulator of the innate immune system, is expressed not only in immune cells, but also in a number of cancer cells. A biological role for TLR4 in cutaneous squamous cell carcinoma (SCC), however, is unclear. In this study, we first examined TLR4 expression and localization in cases of SCC, actinic keratosis (AK) and Bowen's disease (BD) by immunohistochemistry. TLR4 expression was significantly higher in the SCC than in the AK or BD tissues. We then determined the TLR4 expression level in vivo, in 3 histological subtypes of SCC. TLR4 expression in poorly differentiated SCC was significantly lower compared with that of the moderately and well‑differentiated type. In addition, the CD44 immunoreactivity tended to be high in the cell membrane of poorly differentiated SCC. Of note, poorly differentiated SCC is a risk factor of unfavorable outcomes in affected patients. We then assessed the biological role of TLR4 in HSC‑1 and HSC‑5 SCC cells and HaCaT human keratinocytes. TLR4 knockdown by transfection with siRNA accelerated HSC‑1 and HaCaT cell migration and invasion compared to the control siRNA‑transfected cells. TLR4 knockdown resulted in an increased CD44 expression and in an enhanced filopodia protrusion formation, particularly in HSC‑1. On the whole, these results suggest that a reduced TLR4 expression enhances the malignant features in SCC cases and cultured SCC cell lines. TLR4 may thus play an anti‑tumor role in cutaneous SCC.
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http://dx.doi.org/10.3892/ijo.2019.4790DOI Listing
June 2019

Exfoliation of Alveolar Rhabdomyosarcoma Cells in the Ascites of a 50-Year-Old Woman: Diagnostic Challenges and Literature Review.

J Nippon Med Sch 2019 Sep 26;86(4):236-241. Epub 2019 Apr 26.

Department of Integrated Diagnostic Pathology, Nippon Medical School.

Alveolar rhabdomyosarcoma (ARMS) is a nonepithelial tumor with skeletal muscle differentiation and typically affects adolescents and young adults. The cytological features of ARMS in body fluid have not been well characterized, which complicates diagnosis. Here, we describe the cytological features of ARMS in the ascites of a 50-year-old woman with an intra-abdominal mass and abundant ascites. Aspiration cytology of ascitic fluid revealed numerous small discohesive round cells with mild nuclear atypia and prominent nucleoli. Rhabdomyoblastic cells, characteristic of rhabdomyosarcoma, were identified rarely. Cannibalism and 'window' formation, as seen in reactive mesothelial cells, complicated the diagnosis of ARMS. Histological examination established the diagnosis of ARMS, which was confirmed by immunohistochemical expression of myogenic markers. When diagnosing ARMS from effusion samples, the diagnostic problems associated with the morphological similarity of ARMS cells to reactive mesothelial cells should be considered.
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http://dx.doi.org/10.1272/jnms.JNMS.2018_86-404DOI Listing
September 2019

A Case of Rheumatoid Arthritis Presenting with Renal Thrombotic Microangiopathy Probably due to a Combination of Chronic Tacrolimus Arteriolopathy and Severe Hypertension.

Case Rep Nephrol 2019 6;2019:3923190. Epub 2019 Mar 6.

Department of Internal Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan.

A 51-year-old woman with rheumatoid arthritis presented with mild hypertension 20 months after tacrolimus treatment and developing proteinuria 24 months after the treatment. Tacrolimus was discontinued 27 months after the treatment, followed by heavy proteinuria, accelerated hypertension, and deteriorating renal function without ocular fundus lesions as a clinical sign of malignant hypertension. Renal biopsy revealed malignant nephrosclerosis characterized by subacute and chronic thrombotic microangiopathy (TMA), involving small arteries, arterioles, and glomeruli. Focal segmental glomerulosclerosis, probably secondary to chronic TMA, was identified as a cause of heavy proteinuria. The zonal tubulointerstitial injury caused by subacute TMA may have mainly contributed to deteriorating renal function. The presence of nodular hyalinosis in arteriolar walls was indicative of tacrolimus-associated nephrotoxicity. Together with other antihypertensive drugs, administration of aliskiren stabilized renal function with reducing proteinuria. Owing to the preexisting proteinuria prior to severe hypertension and the complex renal histopathology, we postulated that chronic TMA, which was initially triggered by tacrolimus, was aggravated by severe hypertension, resulting in overt renal TMA.
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http://dx.doi.org/10.1155/2019/3923190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431373PMC
March 2019

A Patient with MPO-ANCA-positive IgA Nephropathy Diagnosed with the Clinical Onset of Macrohematuria.

Intern Med 2019 Jul 28;58(14):2051-2056. Epub 2019 Mar 28.

Department of Internal Medicine, Teikyo University School of Medicine, Japan.

A 21-year-old woman presented with renal dysfunction during macrohematuria. A kidney biopsy revealed IgA nephropathy with a small percentage of crescent formation and macrohematuria-associated tubular injury. Macrohematuria-associated acute kidney injury could explain her renal dysfunction. However, she was seropositive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) and showed fibrin deposition around one arteriole. Corticosteroids and mycophenolate mofetil were administered as for ANCA vasculitis, and the serum creatinine, abnormal urinalysis and MPO-ANCA titer all gradually ameliorated. The presence of extra-glomerular vasculitis, which was probably induced by ANCA, suggested that MPO-ANCA was an exacerbating factor for her prolonged renal dysfunction. This condition has so far only rarely been addressed in ANCA-positive IgA nephropathy.
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http://dx.doi.org/10.2169/internalmedicine.2475-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702016PMC
July 2019

Monoclonal Immunoglobulin Deposition Disease and Related Diseases.

J Nippon Med Sch 2019 ;86(1):2-9

Department of Analytic Human Pathology, Nippon Medical School.

Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum, causing monoclonal gammopathy, which leads to various diseases including renal diseases. Therefore, monoclonal gammopathy is frequently associated with kidney diseases, including glomerular and tubulointerstitial diseases. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease (MIDD), AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components are constituted by light chain (myeloma) cast nephropathy, light chain associated Fanconi's syndrome (light chain proximal [crystal] tubulopathy), and crystal-storing histiocytosis. In the present review article, we demonstrate the clinicopathological characteristics of MIDD, which is one of the representative diseases of plasma cell dyscrasias, and discuss various renal diseases with the deposition of monoclonal immunoglobulins or their components in glomeruli and the tubulointerstitium. We recommend that these renal diseases are arranged as one disease category, "renal diseases with deposition of monoclonal immunoglobulins or their components", in order to simplify the understanding of complicated diseases in plasma cell dysplasia.
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http://dx.doi.org/10.1272/jnms.JNMS.2019_86-1DOI Listing
April 2019
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