Publications by authors named "Hirotsugu Hashimoto"

54 Publications

A new classification for the diagnosis of superficial non-ampullary duodenal epithelial tumors using endocytoscopy: a prospective study.

J Gastroenterol Hepatol 2021 Jun 17. Epub 2021 Jun 17.

Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan.

Background And Aim: Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria.

Methods: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification (ECD) was compared with the final histopathological diagnoses.

Results: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared to preoperative biopsy diagnosis (p<0.001, respectively).

Conclusions: This new classification (ECD) allows prediction of the tumor histopathology in real-time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs.
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http://dx.doi.org/10.1111/jgh.15585DOI Listing
June 2021

Cystic Lesion of Dissected Pararectal Lymph Node in a Female Patient With Rectal Carcinoma: A Rare Pattern of Nodal Metastasis Mimicking a Serous Inclusion Cyst.

Int J Surg Pathol 2021 Mar 18:10668969211003959. Epub 2021 Mar 18.

NTT Medical Center Tokyo, Tokyo, Japan.

Nodal metastatic foci of colorectal carcinoma are usually solid nodules. Serous inclusions are occasionally found in lymph nodes, particularly in female patients, and they occasionally form cysts. An 86-year-old woman was treated with laparoscopic low anterior resection and D3 lymph node dissection for advanced rectal carcinoma. A cyst with serous fluid and no necrotic debris was found within one of the dissected pararectal lymph nodes. Histologically, the cyst was lined by low columnar-to-cuboid epithelium with mild nuclear atypia, mimicking a serous inclusion cyst. Immunohistochemically, the epithelial cells were positive for caudal type homeobox 2 and negative for Wilms' tumor suppressor gene1. Immunohistochemistry for p53 showed a diffuse strong positivity, indicating a mutant as seen in primary rectal carcinoma. Thus, the nodal cystic lesion was confirmed to be a metastatic lesion. It is important to carefully assess a nodal cystic lesion to confirm whether it is benign or malignant.
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http://dx.doi.org/10.1177/10668969211003959DOI Listing
March 2021

Large duodenal pyloric gland adenoma successfully resected by endoscopic submucosal dissection.

Clin J Gastroenterol 2021 Apr 4;14(2):538-541. Epub 2021 Mar 4.

Department of Gastrointestinal Endoscopy, NTT Medical Center Tokyo, 5-9-22 Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.

A 71-year-old woman was given a barium meal examination as part of a workup for recurring melena and iron deficiency anemia (IDA), and it revealed a large duodenal polyp measuring 60 mm in diameter. Subsequent upper gastrointestinal endoscopy showed a large pedunculated polyp in the duodenal bulb. Magnifying endoscopy with narrow-band imaging (NBI) showed that the lesion consisted of a regular enlarged intervening part between crypts of the epithelium that resembled gastric mucosa. Although the lesion was suspected of being benign, it was resected by endoscopic submucosal dissection (ESD) to prevent the progression of the IDA. The pathology examination revealed the proliferation of mildly irregular-shaped or dilated glands lined by cuboidal cells and low columnar cells in the submucosa. The gastric glands were immunohistochemically positive for MUC6, suggesting pyloric gland differentiation. The lesion was covered by a foveolar-type epithelium, and we made a diagnosis of pyloric gland adenoma (PGA). PGAs are most common in the stomach, and they are rare in the duodenum, where endoscopic treatment is technically challenging. Here we report a case of large duodenal PGA successfully resected by ESD. Since part of PGAs has been reported to be associated with adenocarcinoma, minimally invasive treatment strategies are desirable to reduce the risk of progression to carcinoma.
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http://dx.doi.org/10.1007/s12328-021-01367-wDOI Listing
April 2021

CD10-Negative Primary Breast Follicular Lymphoma: A Rare Case of Primary Breast Lymphoma With an Atypical Immunophenotype Mimicking Marginal Zone Lymphoma.

Int J Surg Pathol 2021 Jun 30;29(4):400-403. Epub 2020 Nov 30.

NTT Medical Center Tokyo, Tokyo, Japan.

In this article, we report the case of a 78-year-old woman who consulted our hospital for a right breast mass detected on mammography during her cancer screening. Biopsy specimens showed atypical lymphocytic infiltration with a follicle-like growth pattern, suggesting a follicular lymphoma (FL). Immunohistochemically, the atypical lymphoid cells were diffusely and strongly positive for CD20, BCL2, and BCL6, but negative for CD10. IGH- translocation was confirmed by fluorescence in situ hybridization analysis, leading to the diagnosis of primary breast FL. The most important differential diagnosis of this case was marginal zone lymphoma (MZL), which usually shows a CD10/BCL2 immunophenotype and is one of the common histological types in primary breast lymphomas. FLs with an atypical immunophenotype exist in a certain percentage of patients. Therefore, FL is considered to be a heterogeneous entity. It is important to distinguish FL from MZL in primary breast lymphomas because FLs may have a worse prognosis than MZLs.
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http://dx.doi.org/10.1177/1066896920977690DOI Listing
June 2021

Clinicopathologic Characteristics of Esophageal Ectopic Sebaceous Glands: Chronological Changes and Immunohistochemical Analysis.

Int J Surg Pathol 2021 Jun 26;29(4):378-384. Epub 2020 Aug 26.

NTT Medical Center Tokyo, Tokyo, Japan.

Esophageal ectopic sebaceous glands are very rare lesions. A series of 5 cases in a single report has been the maximum number described in the English literature to date. We conducted a clinicopathologic study of 8 cases of esophageal ectopic sebaceous glands. The median patient age at the time of diagnosis was 60 years (range, 50-71 years), and 7 of the 8 patients were male. A focal lesion was observed in 7 cases, whereas 1 case exhibited multiple lesions throughout the esophagus. Four patients had previously undergone upper gastrointestinal endoscopy; in 3 patients, the focal lesion had not been detected. After diagnosis, 3 cases showed spontaneous regression at least once. Immunohistochemically, sebocytes of all 8 cases were negative for the estrogen receptor (ER) and the progesterone receptor (PgR), whereas sebocytes of 5 cases were positive for the androgen receptor (AR). Basal/parabasal cells were positive for AR, ER, and PgR in 5, 7, and 4 cases, respectively. GATA3 was expressed in the sebocytes and basal/parabasal cells of 6 out of 7 available cases, whereas all of 7 available cases were negative for mammaglobin and GCDFP15. Our report provides the basic clinicopathologic characteristics of esophageal ectopic sebaceous glands by the largest case series reported in English literature to date. Furthermore, the chronological changes, particularly spontaneous regression, and immunohistochemical expression of hormone receptors and GATA3 are compatible with lesions resulting from congenital misplacement under hormonal regulation. Therefore, they seem to be congenital misplacements detectable as a result of hormonal stimulated growth.
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http://dx.doi.org/10.1177/1066896920951844DOI Listing
June 2021

Uterine cervical squamous cell carcinoma with reactive multinucleated giant cells expressing cluster of differentiation 204: A case report and literature review.

J Obstet Gynaecol Res 2020 Oct 10;46(10):2174-2178. Epub 2020 Aug 10.

Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo, Japan.

Uterine cervical squamous cell carcinoma (SCC) with reactive multinucleated giant cells (MGC) is extremely rare. Here we present the case of a 49-year-old woman treated with radical hysterectomy, bilateral adnexectomy and lymph node dissection. Histologically, the cervical tumor was diagnosed as nonkeratinizing SCC of pT1b1N0M0, with negative surgical margin. Many MGC including osteoclast-like giant cells with immunohistochemical expression of cluster of differentiation 204, a marker for the M2 macrophage, were present around the tumor nests. The patient received postoperative radiation therapy and achieved 22 months of disease-free survival after the surgery. M2 macrophages promote aggressiveness of the carcinoma and it is suggested that SCC of the cervix with reactive MGC might have poor prognosis; however, our case paradoxically showed a favorable course. From literature review of six cases, including our case, the effect of MGC-reaction may vary with respect to other factors, such as age, cancer stage or histological type.
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http://dx.doi.org/10.1111/jog.14404DOI Listing
October 2020

Simple scoring system for the diagnosis of superficial non-ampullary duodenal epithelial tumors.

Dig Endosc 2021 Mar 28;33(3):399-407. Epub 2020 Aug 28.

Divisions of, Division of, Gastrointestinal Endoscopy, NTT Medical Center Tokyo, Tokyo, Japan.

Background And Aims: Differentiating superficial non-ampullary duodenal epithelial tumors (SNADETs) that harbor malignant potential is important. We developed a simple scoring system and investigated whether it enables the differentiation of low-grade adenoma and high-grade adenoma/adenocarcinoma.

Patients And Methods: We retrospectively enrolled 197 consecutive patients with 207 SNADETs who underwent endoscopic resection at NTT Medical Center Tokyo between March 2016 and May 2019. Endoscopic findings were compared between Vienna Classification (VCL) C3 and C4/5 lesions. A multivariate logistic regression analysis was performed to develop a scoring system to identify VCL C4/5 lesions. The efficacy of our scoring system was elucidated among five novice and five expert endoscopists.

Results: Of 207 SNADETs, 66 and 141 lesions were pathologically diagnosed as VCL C3 and C4/5. A multivariate logistic regression analysis identified a tumor diameter of 10-19 mm (OR, 3.81; 95% CI, 1.02-14.2; P = 0.04), a tumor diameter ≥20 mm (OR, 95.2; 95% CI, 10.4-871.0; P < 0.001), a red color (OR, 14.5; 95% CI, 3.55-59.6; P < 0.001), the presence of irregular surface pattern (OR, 12.4; 95% CI, 3.00-51.4; P < 0.001), and the presence of irregular vessel pattern (OR, 13.7; 95% CI, 4.03-46.6; P < 0.001) as independent significant predictors of VCL C4/5. Considering these results, we developed a scoring system. Using an appropriate cutoff value, the diagnostic accuracy, sensitivity and specificity were calculated as 92%, 95% and 93%. The average diagnostic accuracy did not differ between novice and expert endoscopists (86% vs 87%, P = 0.76).

Conclusions: Our scoring system was useful for differentiating VCL C3 and C4/5 lesions. UMIN Clinical Trials (No. 000039063).
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http://dx.doi.org/10.1111/den.13762DOI Listing
March 2021

Progressively increasing density of the solid center of a ground-glass nodule in a solitary pulmonary capillary hemangioma: A case report.

Pathol Int 2020 Aug 5;70(8):568-573. Epub 2020 May 5.

Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo, Japan.

Solitary pulmonary capillary hemangiomas (SPCHs) are recently recognized, rare benign lesions that form solitary nodules owing to capillary proliferation. These lesions are usually detected incidentally as small ground-glass nodules (GGNs) on computed tomography (CT), and progressively enlarge over time. The radiological distinction from peripheral lung cancers is particularly challenging. However, to date, there have been no reports on progressive changes in the central density of SPCH on CT. An asymptomatic 49-year-old man was referred to our hospital for an abnormal shadow that was detected on chest CT during medical check-up. He was subsequently followed-up with chest CT. The nodule increased in size, and the central area became progressively denser. He underwent surgery 5 years and 10 months after the first visit owing to suspicion of lung cancer. Despite the collapse of the surgical specimen by artifacts, histopathological examination revealed a diagnosis of SPCH; collagenous fibers were found in the walls of the intralesional capillaries. The patient is presently alive without any recurrence, 6 months after the operation. In this case, the SPCH demonstrated a GGN with progressively increasing density of the central solid area on the CT. This remarkable feature made the preoperative distinction from lung cancer particularly difficult.
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http://dx.doi.org/10.1111/pin.12945DOI Listing
August 2020

Colonic Neurogenic Lesion: An Admixture of Mucosal Neurofibromatous Lesion and Submucosal Ganglioneuromatous Lesion With Transition.

Int J Surg Pathol 2020 Aug 6;28(5):563-568. Epub 2020 Feb 6.

NTT Medical Center Tokyo, Tokyo, Japan.

Benign neural tumors or tumor-like lesions are rarely detected in the gastrointestinal tract. In this article, we present the case of a neural lesion of the sigmoid colon, which was incidentally detected in a 68-year-old man treated with laparoscopic low anterior resection for an advanced carcinoma of the rectosigmoid junction. Within the resected specimen, a submucosal tumor-like protruding lesion was found in the sigmoid colon. Histologically, the growth was composed of mucosal neurofibromatous and submucosal ganglioneuromatous lesions, between which there was transition. Immunohistochemical analysis revealed a rupture of the perineurium in the area of transition, along with a proliferation of Schwann cells and supporting cells extending into the deep mucosa. This transition indicated that the mucosal and submucosal lesions comprised a single lesion, and that a diagnosis of neurofibroma or ganglioneuroma would be inadequate in this case. Because we could not classify it as an established single entity, we diagnosed the mass as an unclassifiable colonic neurogenic lesion. In summary, we report the case of an extremely rare occurrence of an unclassifiable colonic neurogenic lesion comprising an admixture of transitioning mucosal neurofibromatous and submucosal ganglioneuromatous lesions.
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http://dx.doi.org/10.1177/1066896920904158DOI Listing
August 2020

Arteritis and Plexiform Lesion in Intralobar Pulmonary Sequestration: The First Case With Such Two Distinct Complex Lesions Associated With Local Pulmonary Hypertension.

Int J Surg Pathol 2020 May 6;28(3):321-324. Epub 2019 Nov 6.

NTT Medical Center Tokyo, Tokyo, Japan.

In intralobar pulmonary sequestrations, vascular changes similar to those in pulmonary hypertension (PH) are generally observed, such as intimal proliferation and plexiform lesions. However, to our knowledge, a sequestrated lung manifesting vascular changes with both arteritis and a plexiform lesion has never been reported. A 25-year-old man was diagnosed with intralobar pulmonary sequestration. Pathologically, both arteritis and a plexiform lesion were observed in the sequestrated lung. Systemic vasculitis syndrome was clinically excluded, and the pathological findings appeared to be associated with local PH. Arteritis is an extremely rare finding; only one case of arteritis associated with local PH has been reported in intralobar sequestration. In this case, the artery near the plexiform lesion had milder inflammation and fibrosis, suggesting that the arteritis formed prior to the plexiform lesion. This is the first case of arteritis and a plexiform lesion co-occurring in intralobar pulmonary sequestration associated with local PH. This case may shed light on the formation of plexiform lesions and their association with arteritis.
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http://dx.doi.org/10.1177/1066896919886663DOI Listing
May 2020

Myocardial calcification in a patient with B-lymphoblastic leukemia accompanied by tumor lysis syndrome.

Cardiovasc Pathol 2019 Nov - Dec;43:107146. Epub 2019 Aug 7.

Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo, Japan; Faculty of Healthcare, Tokyo Healthcare University, Tokyo, Japan.

Myocardial calcification, a rare disease that leads to chronic or acute heart failure and with a poor prognosis, occurs in patients with abnormal calcium-phosphorus metabolism. The association between myocardial calcification and tumor lysis syndrome has not been reported to date. A 50-year-old man with hyperthermia and general malaise presented to our hospital and was clinically diagnosed with B-lymphoblastic leukemia (B-ALL) and febrile neutropenia accompanied by septic shock. Prednisolone was administered for tumor reduction. Two to three hours later, electrocardiography demonstrated ST elevation in V4-6, and blood tests showed elevated levels of cardiac enzymes. Transthoracic echocardiogram revealed diffuse severe hypokinesis with decreased left ventricular ejection fraction. Additionally, blood tests showed that serum phosphorus level increased to 8.0 mg/dl, which was likely due to tumor lysis syndrome. Circulatory and respiratory failure due to left heart failure progressed, and he died 3 days after administration of prednisolone. Pathological autopsy revealed diffuse proliferation of atypical B-lymphoblasts in the bone marrow, which led to the pathological diagnosis of B-ALL, accompanied by necrosis. On the cut surface of the heart, the left ventricle was dilated, and patchy yellowish-brown areas were present in the epicardial-side of the myocardium and spread through the circumferential wall of the left ventricle and interventricular septum. Microscopically, myocardial fibers were granularly basophilic in that area and were revealed as calcium deposits by Von Kossa staining. He was diagnosed with myocardial calcification. The drastic increase in the serum phosphorus level caused by tumor lysis syndrome seemed to be associated with myocardial calcification.
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http://dx.doi.org/10.1016/j.carpath.2019.07.005DOI Listing
February 2020

Cerebral amyloid-β-related angiitis without cerebral microbleeds in a patient with subarachnoid hemorrhage.

Cardiovasc Pathol 2019 Sep - Oct;42:36-40. Epub 2019 May 25.

Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo, Japan; Faculty of Healthcare, Tokyo Healthcare University, Tokyo, Japan.

Amyloid-β-related angiitis (ABRA), a subtype of cerebral amyloid angiopathy (CAA), is vasculitis occurring in relation to amyloid-β (Aβ) deposition in the walls of intracranial blood vessels. ABRA is presumed to be caused by some immune response to the deposited Aβ. An 81-year-old man on oral anticoagulant therapy complained of headache, nausea, and difficulty with standing after a head injury. Head computed tomography revealed subcortical bleeding in the right temporoparietal lobe, and 3 days after admission, magnetic resonance imaging (MRI) showed subarachnoid hemorrhage (SAH) around the hematoma. Cerebral microbleeds, a characteristic of CAA, were not detected on MRI. On worsening of his symptoms, intracranial brain biopsy and hematoma removal were performed. Intraoperative rapid diagnosis with a frozen section suspected vasculitis, which enabled the prompt initiation of steroid therapy. He was pathologically diagnosed with ABRA (granulomatous angiitis) using a formalin-fixed paraffin-embedded section. Vasculitis was prominent around blood vessels in the pia matter covering the cerebrum. In this case, the inflammatory cells seemed to appear via the subarachnoid space following cerebral hemorrhage and SAH. ABRA seemed to be developed by intracranial hemorrhage in this case.
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http://dx.doi.org/10.1016/j.carpath.2019.05.004DOI Listing
December 2019

Intrahepatic Carcinosarcoma With Cholangiocarcinoma Elements and Prominent Bile Duct Spread.

Int J Surg Pathol 2019 Dec 17;27(8):900-906. Epub 2019 Jun 17.

NTT Medical Center Tokyo, Tokyo, Japan.

Carcinosarcomas with elements of cholangiocarcinoma and sarcoma are rare and have a poor prognosis. The spreading pattern and radiological findings of these lesions remain unclear. A 74-year-old man presented with a high γ-glutamyl transferase level. Magnetic resonance imaging revealed dilation of the right intrahepatic and common bile ducts, consistent with an intraductal papillary neoplasm of the bile duct (IPNB), and diffusion-weighted imaging (DWI) indicated an area of high signal intensity in the intrahepatic bile duct. Bile duct biopsy yielded a small amount of atypical spindle cells, and the patient underwent a right hepatectomy. Microscopically, the tumor contained cholangiocarcinoma and sarcomatous components, including osteosarcoma and leiomyosarcoma, leading to a diagnosis of intrahepatic carcinosarcoma. The tumor spread primarily through the intrahepatic bile duct. An accurate radiological diagnosis of carcinosarcoma was challenging, given the apparent similarities with IPNB. The findings from DWI and pathology of a bile duct biopsy may assist with preoperative diagnosis.
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http://dx.doi.org/10.1177/1066896919855766DOI Listing
December 2019

Aortogenic Embolic Stroke Diagnosed by a Pathological Examination of Endovascularly Removed Thrombus: An Autopsy Report.

Intern Med 2019 Oct 7;58(19):2851-2855. Epub 2019 Jun 7.

Department of Diagnostic Pathology, NTT Medical Center Tokyo, Japan.

Complex aortic atheroma is a high-risk factor for recurrent embolic stroke. An accurate identification of stroke etiology is clinically important; however, it can be challenging. A 91-year-old man with atrial fibrillation was diagnosed with cardioembolic stroke and treated with mechanical thrombectomy. The removed thrombus microscopically contained foamy cells, suggesting an atheroembolism. An autopsy revealed an atherosclerotic lesion with ulceration, located in the aortic arch. At the lesion, the plaque had microscopically ruptured into the lumen. We therefore concluded that the aortic atherosclerotic lesion was the embolic source. Removed thrombi should be pathologically examined even if a cardioembolic stroke is clinically suspected.
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http://dx.doi.org/10.2169/internalmedicine.2857-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815896PMC
October 2019

Cerebral Thromboembolism after Lobectomy for Lung Cancer: Pathological Diagnosis and Mechanism of Thrombus Formation.

Cancers (Basel) 2019 04 5;11(4). Epub 2019 Apr 5.

Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.

Lung cancer is the leading cause of cancer-related deaths worldwide. Although molecular therapies have emerged as efficacious strategies for the treatment of lung cancer, surgical resection is still recommended as a radical therapeutic option. Currently, lobectomy is regarded as the most reliable radical treatment of primary lung cancer. Among the various complications after lobectomy, cerebral thromboembolism requires attention as a life-threatening complication during the early postoperative period. It occurs in 0.2⁻1.2% of surgical cases of lung cancer and typically develops following left upper lobectomy with a long pulmonary vein stump (PVS). PVS-associated thrombosis is known to cause cerebral thromboembolism after such procedures; however, distinguishing this specific complication from that caused by postoperative atrial fibrillation is challenging. We summarize herein the diagnostic pathology of thrombus formation in accordance with its thrombogenic mechanism. We focus on the potential utility of the pathological assessment of thrombectomy specimens. The morphological information obtained from these specimens enables the presumption of thrombogenic etiology and provides useful clues to both select an appropriate pharmacotherapy and determine a follow-up treatment for cerebral thromboembolism.
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http://dx.doi.org/10.3390/cancers11040488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521235PMC
April 2019

Enterocolic lymphocytic phlebitis with marked myointimal hyperplasia and perivenous concentric fibrosis.

Cardiovasc Pathol 2019 May - Jun;40:68-71. Epub 2019 Mar 6.

Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo, Japan; Faculty of Healthcare, Tokyo Healthcare University, Tokyo, Japan.

Enterocolic lymphocytic phlebitis (ELP) is a rare enteropathy characterized by lymphocytic phlebitis of the mesenteric veins without arteritis. Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare disease similar to ELP, characterized by myointimal hyperplasia that constricts the lumen of veins, causing mucosal injury. A 62-year-old man with chief complaint of abdominal pain was treated by partial resection of the ileum after 3 months of conservative therapy. The pathologic diagnosis was ELP with prominent myointimal hyperplasia. Histologically, the lesion consisted of lymphocytic infiltration into the vein accompanied by prominent myointimal hyperplasia and perivenous concentric fibrosis, which are characteristics shared by ELP and IMHMV. The observations in this case suggest that some of ELP and IMHMV may belong to the same disease spectrum. Furthermore, perivascular concentric fibrosis was a remarkable observation that may contribute to differential diagnosis between ELP and "true" IMHMV.
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http://dx.doi.org/10.1016/j.carpath.2019.02.006DOI Listing
July 2019

Mesenchymal tumors of the lung: diagnostic pathology, molecular pathogenesis, and identified biomarkers.

J Thorac Dis 2019 Jan;11(Suppl 1):S9-S24

Division of Pathology, The Cancer Institute, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Lung cancers are mainly composed of epithelial tumors such as carcinomas. Since mesenchymal tumors that arise in the lung are very rare, they have garnered little attention. The 2015 World Health Organization (WHO) classification of lung tumors has undergone revision, not only for carcinomas but also for mesenchymal tumors. The current version now includes PEComatous tumors, myoepithelial tumors, and pulmonary myxoid sarcomas with translocation as new disease entities. To date, no review article has comprehensively summarized what is known about pulmonary mesenchymal tumors in accordance with the latest WHO classification. In this review, we attempt to summarize the data about these tumors in line with the 2015 WHO classification (except for pediatric tumors), focusing on their diagnostic pathology, molecular pathogenesis, and identified biomarkers for differential diagnoses. We also address the recently recognized pulmonary mesenchymal tumors that have not yet been included in the WHO classification. An increased understanding of the molecular characteristics of pulmonary mesenchymal tumors has the potential to provide clinicians with the best therapeutic options for patients with these tumors.
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http://dx.doi.org/10.21037/jtd.2018.12.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353741PMC
January 2019

Intramucosal colorectal carcinoma with lymphovascular invasion: clinicopathological characteristics of nine cases.

Histopathology 2019 Jun;74(7):1055-1066

Department of Diagnostic Pathology, NTT Medical Center Tokyo, Tokyo, Japan.

Aims: Recent studies have provided the concept of invasive intramucosal colorectal carcinoma (CRC), and a case of intramucosal CRC with lymphatic invasion has been reported; however, the characteristics of such cases and the risk of lymph node metastasis have never been investigated. Therefore, we aimed to assess the pathological characteristics of intramucosal CRCs with lymphovascular invasion as well as the possibility of lymph node metastasis as an indication for additional surgery.

Methods And Results: To delineate the histological features of intramucosal CRCs with lymphovascular invasion, we analysed several histological features and compared their incidence among nine such cases, as well as 20 other cases of intramucosal CRCs without lymphovascular invasion. High-grade tumour budding and a pattern of 'eosinophilic cytoplasm and round nuclei with inflammatory reaction (ERI)' were morphological characteristics of intramucosal CRCs with lymphovascular invasion, compared with those without lymphovascular invasion (both P < 0.05). Among the seven lymph node-dissected cases of intramucosal CRCs with lymphovascular invasion, none showed lymph node metastasis.

Conclusions: In intramucosal CRCs with lymphovascular invasion, high-grade tumour budding and the 'ERI' pattern are morphological characteristics that are distinct from those of non-invasive CRC, which is synonymous with high-grade dysplasia. Further studies using a larger number of cases by focusing on the above-mentioned histological pattern are expected to clarify the potential of lymph node metastasis of such cases.
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http://dx.doi.org/10.1111/his.13826DOI Listing
June 2019

Difference in immunohistochemical characteristics between Takayasu arteritis and giant cell arteritis: It may be better to distinguish them in the same age.

Mod Rheumatol 2019 Nov 18;29(6):992-1001. Epub 2019 Feb 18.

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

This study aimed to compare Takayasu arteritis (TAK) with giant cell arteritis (GCA) through immunohistochemistry principally of inflammatory cells; these two disorders may be on the spectrum within a single disease state. Nine TAK and 5 GCA surgically resected vessel specimens were selected. TAK specimen was divided into each three acute-, chronic-, and healed-phase samples based on intimal and adventitial thickening. Immunohistochemical analysis was performed of smooth muscle cells and inflammatory cells including lymphocytes, plasma cells, macrophages, and dendritic cells, where three healed-phase TAK specimens were excluded due to paucity of inflammation. Immunopositive cells per three different fields in intima, media, and adventitia were counted in each specimen, and their numbers in these three layers along with total 3 layers were compared between the two disorders. Intimal smooth muscle maturity estimated by ratio of h-Caldesmon cells to α-SMA cells significantly increased in chronic- and healed- over acute-phase increases in TAK. Mann-Whitney tests demonstrated significantly more adventitial lymphoplasmacytic infiltration and less intimal fascin dendritic cells, as well as overall more CD8 T-cells, more CD20 B-cells and lower CD4/8 ratio in TAK than in GCA. Different inflammatory involvement is suggested in the pathogenesis of TAK and GCA.
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http://dx.doi.org/10.1080/14397595.2019.1570999DOI Listing
November 2019

Colon Metastasis From Microscopic Serous Carcinoma of the Fallopian Tube Fimbria Mimicking a Primary Colon Cancer.

Int J Surg Pathol 2019 Jun 20;27(4):390-395. Epub 2019 Jan 20.

1 NTT Medical Center Tokyo, Tokyo, Japan.

Metastatic diseases rarely develop in the colorectum, and diagnosing colorectal metastasis by biopsy without history of a malignant tumor or clinical information of a primary tumor is challenging. A 65-year-old woman with a 6-month history of constipation and diarrhea was admitted to our hospital and diagnosed with rectosigmoid colonic micropapillary carcinoma. Low anterior resection was performed after neoadjuvant chemotherapy. Because the lipoleiomyoma in the uterus obstructed the operator's vision, total hysterectomy and bilateral salpingo-oophorectomy were performed. Examination of the colon and adnexa, together with immunohistochemical studies, revealed that the colonic tumor was actually serous carcinoma that had metastasized from the left fimbria of the fallopian tube. Retrospective immunohistochemical examination of the colon biopsy specimen suggested carcinoma with a Müllerian immunophenotype. When a colon biopsy reveals carcinoma with an invasive micropapillary pattern without a component of conventional tubular adenocarcinoma, immunohistochemical examination should be performed to rule out the possibility of metastasis.
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http://dx.doi.org/10.1177/1066896918824028DOI Listing
June 2019

Cerebral Embolism Caused by Thrombus in the Pulmonary Vein Stump after Left Lower Lobectomy: A Case Report and Literature Review.

Intern Med 2019 May 18;58(9):1349-1354. Epub 2018 Dec 18.

Department of Cerebrovascular Medicine, NTT Medical Center Tokyo, Japan.

Cerebral embolism after left upper lobectomy caused by a thrombus in the pulmonary vein stump (PVS) is a serious complication. However, it is unclear if cerebral embolism can develop after other types of lobectomy. We present a case of a 68-year-old man with cerebral embolism after left lower lobectomy with a longer PVS than normal. There were no clinically suspected sources for the thrombus except for the PVS. This thrombus seemed to have formed in the PVS. The endovascularly removed thrombus contained scattered nuclear debris around neutrophils, suggesting a physiological response caused by tissue injury.
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http://dx.doi.org/10.2169/internalmedicine.1962-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543232PMC
May 2019

Clinical Outcomes of Patients with Small Rectal Neuroendocrine Tumors Treated Using Endoscopic Submucosal Resection with a Ligation Device.

Digestion 2019 14;99(1):72-78. Epub 2018 Dec 14.

Department of Gastroenterology, NTT Medical Center Tokyo, Tokyo, Japan,

Background/aims: The therapeutic strategies for small rectal neuroendocrine tumors (NETs) have not been standardized. We examined the efficacy and safety of endoscopic submucosal resection with a ligation device (ESMR-L) and the long-term outcomes after endoscopic treatment.

Methods: A total of 181 patients with rectal NETs <10 mm who were treated between May 2002 and May 2017 were retrospectively enrolled. All the lesions had been resected using ESMR-L, and the follow-up strategies were determined according to the pathological examinations. The long-term outcomes after a 53-month follow-up period were also evaluated.

Results: R0 resection was achieved in 180 cases (99.4%). Lymphovascular invasion was confirmed in 67 cases (37.0%), while a curative resection was achieved in 114 cases (63.0%). One perforation (0.6%) and 11 cases with delayed bleeding (6.1%) were observed. A multivariate logistic regression analysis revealed that a tumor size > 5 mm (OR 2.06; 95% CI 1.04-4.08, p = 0.04) was a significant independent predictor of the presence of lymphovascular invasion. Of the 67 patients with non-curative resections, 11 patients underwent additional surgery; lymph node metastasis was confirmed in 2 cases (18.2%). No local or distant metastases were observed during the follow-up period in 77 patients with a curative resection, 9 patients who received additional surgery, and 50 patients with non-curative resections.

Conclusion: ESMR-L is an easy, safe and effective treatment for rectal NETs <10 mm in diameter, and the prognosis of patients seems to be good, despite a relatively high rate of lymphovascular invasion.
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http://dx.doi.org/10.1159/000494416DOI Listing
April 2019

Mucosal Schwann Cell Hamartoma of the Rectosigmoid Junction: A Rare Lesion Mimicking Mucosal Prolapse Syndrome and Other Neural Lesions.

Int J Surg Pathol 2019 Aug 12;27(5):515-517. Epub 2018 Dec 12.

1 NTT Medical Center Tokyo, Tokyo, Japan.

In this article, we report the case of a 40-year-old woman with a sessile polyp of the rectosigmoid junction that underwent endoscopic resection. The resected specimen showed spindle cell proliferation with eosinophilic cytoplasm between mucosal crypts, mimicking mucosal prolapse syndrome. However, these were immunohistochemically positive for S-100, indicating neural cell origin. As neural polypoid lesion of the rectum, neurofibroma, perineurioma, schwannoma, and mucosal Schwann cell hamartoma were in the differential diagnosis. Histology and additional immunohistochemistry confirmed mucosal Schwann cell hamartoma. Mucosal Schwann cell hamartoma of the rectosigmoid junction or rectum can be a histological mimic of mucosal prolapse syndrome and other S-100 positive neural cell lesions; however, the lesion in the present case was correctly diagnosed with histology and immunohistochemistry.
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http://dx.doi.org/10.1177/1066896918818897DOI Listing
August 2019

An estrogen receptor-positive locally aggressive smooth muscle neoplasm of the transverse colon: A case report.

Medicine (Baltimore) 2018 Nov;97(46):e13250

Department of Diagnostic Pathology, NTT Medical Center Tokyo.

Rationale: Extrauterine leiomyomas (LMs) in women are often positive for the estrogen receptor (ER); however, almost all extrauterine leiomyosarcomas (LMSs) are negative for ER. Invasive smooth muscle neoplasms (SMNs) of the gastrointestinal tract walls are very rare and those ER statuses have not been well studied.

Patient Concerns: A 48-year-old woman presented to our hospital with a 10 years history of recurrent severe abdominal pain and diarrhea lasting about an hour, with frequency of about twice per year. She was clinically diagnosed with a submucosal tumor (SMT) of the transverse colon and underwent a partial transverse colectomy.

Diagnosis: A colonoscopy revealed a 30-mm SMT in the transverse colon. A contrast abdominal computed tomography detected a 21-mm mass with significant late phase enhancement in the transverse colon and the lesion was clinically diagnosed as an SMT. Post-operative pathology confirmed a diagnosis of ER-positive locally aggressive SMN.

Interventions: The patient underwent laparoscopic partial transverse colectomy.

Outcomes: The patient received no adjuvant therapy postoperatively. The patient has remained disease-free without recurrence 13 months after the surgery.

Lessons: This is the first case of an ER-positive invasive SMN in the gastrointestinal tract. It highlights the difficulty in classifying some gastrointestinal SMNs as either LMs or LMSs and the importance of ER status in SMNs.
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http://dx.doi.org/10.1097/MD.0000000000013250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257419PMC
November 2018

Focal segmental glomerulosclerosis lesion associated with inhibition of tyrosine kinases by lenvatinib: a case report.

BMC Nephrol 2018 10 19;19(1):273. Epub 2018 Oct 19.

Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.

Background: Lenvatinib is a tyrosine kinase inhibitor with novel binding ability. It is considered the standard of care for metastatic thyroid cancer; moreover, whether it is indicated for other malignant tumors has been examined. Lenvatinib increases the risk of kidney injury in some patients. In comparison with sorafenib, which is a conventional tyrosine kinase inhibitor (TKI), lenvatinib results in more side effects, including hypertension and proteinuria. We describe a case of secondary focal segmental glomerulosclerosis (FSGS) that developed following treatment of metastatic thyroid cancer with lenvatinib and reviewed the mechanisms of renal impairment.

Case Presentation: We describe a patient with metastatic thyroid cancer who developed hypertension, nephrotic syndrome, and acute kidney injury after 3 months of lenvatinib treatment. Renal biopsy results revealed that 7 of 16 glomeruli indicated complete hyalinization, and that the glomeruli with incomplete hyalinization showed FSGS due to a vascular endothelial disorder and podocyte damage, which seemed to have been induced by lenvatinib treatment. These findings were similar to those of renal impairment treated with conventional TKIs. Although lenvatinib treatment was discontinued, up to 15 months were required to achieve remission of proteinuria, thus leading to chronic kidney disease with hyalinized lesions.

Conclusions: To the best of our knowledge, this is the first reported case of secondary FSGS by lenvatinib treatment. Renal impairment treated with TKIs is commonly associated with minimal change nephrotic syndrome/FSGS findings, and it is suggested that renal involvement with TKI is different from that with the vascular endothelial growth factor ligand. Overexpression of c-mip due to TKI causes disorders such as podocyte dysregulation and promotion of apoptosis, which cause FSGS. Lenvatinib may result in FSGS by a similar mechanism with another TKI and could cause irreversible renal impairment; therefore caution must be used. It is essential to monitor blood pressure, urinary findings, and the renal function.
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http://dx.doi.org/10.1186/s12882-018-1074-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194623PMC
October 2018

Thrombus Reformation in the Pulmonary Vein Stump Confirmed 16 Months After Cerebral Embolism on the Day After Left Upper Lobectomy for Lung Cancer.

J Stroke Cerebrovasc Dis 2018 Oct 2;27(10):e225-e227. Epub 2018 Aug 2.

Department of Cerebrovascular Medicine, NTT Medical Center Tokyo, Tokyo, Japan. Electronic address:

Cerebral embolism is a very serious complication after lung cancer surgery. In such cases, cerebral embolism is caused by a thrombus formed in the pulmonary vein stump. Most such cases have been reported to occur within 10 days after left upper lobectomy. The patients were treated with anticoagulation therapy to prevent the recurrence of cerebral embolism, and recurrence or thrombus reformation has not been reported to the best of our knowledge. We present a 68-year-old man with a cerebral embolism detected on the day after left upper pulmonary lobectomy for lung cancer. The patient was treated with unfractionated heparin and his neurological symptoms improved. Heparin treatment was subsequently changed to aspirin for the prevention of recurrence; however, thrombus formation in the vein stump was asymptomatically confirmed 16 months after the surgery by contrast-enhanced computed tomography. This is the first case to our knowledge of thrombus reformation in the pulmonary vein stump after a cerebral embolism associated with lung cancer surgery. In our case, anticoagulation therapy was not continued to prevent recurrence, and antiplatelet therapy was performed instead, which might be associated with the thrombus reformation.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.019DOI Listing
October 2018

Good's syndrome with clinical manifestation after thymectomy: A case report.

Respir Med Case Rep 2018 27;24:89-91. Epub 2018 Apr 27.

Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa-ku, Tokyo, Japan.

Good's syndrome is a rare condition of immunodeficiency that is characterized by thymoma and hypogammaglobulinemia. A 74-year-old Japanese woman underwent total thymothymectomy for type AB thymoma (2015 WHO classification). She developed recurrent infectious diseases caused by (bacteremia), (pneumonia and bacteremia) and (bacteremia) in the year after thymectomy. The serum levels of immunoglobulin were significantly low (IgG 157mg/dL), which suggested that her infectious diseases were associated with Good's syndrome. Although she began receiving intravenous immunoglobulin every four weeks, she died of pneumonia a week after the second administration of immunoglobulin. When physicians encounter patients with recurrent infection who have a medical history of thymoma, the detection of hypogammaglubulinemia can be a key clue to the diagnosis of Good's syndrome.
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http://dx.doi.org/10.1016/j.rmcr.2018.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010670PMC
April 2018

Membranoproliferative glomerulonephritis-like findings for TAFRO syndrome, associated with an anterior mediastinal tumor: A case report.

Medicine (Baltimore) 2018 Jun;97(24):e11057

Department of Hypertension and Nephrology Department of Diagnostic Pathology, NTT Medical Centre Tokyo, Higasi-Gotanda, Shinagawa-ku, Tokyo, Japan.

Rationale: TAFRO syndrome is a systemic inflammatory disease proposed recently from Japan. The cause of TAFRO syndrome is unclear. Moreover, the disease characteristics and kidney pathology are yet unknown well and there are few cases. Herein, we report a patient with TAFRO syndrome and present the features of the renal histopathology.

Patient Concerns: A 55-year-old woman presented to our hospital with the main complaint of subacute dyspnoea.

Diagnosis: Physical findings included a low-grade fever and generalised oedema. A blood test showed anaemia, coagulation abnormalities, hypoproteinaemia, impaired renal function, proteinuria, and elevated alkaline phosphatase (ALP), C-reactive protein (CRP), interleukin-6 (IL-6). Chest and abdominal computed tomography showed an anterior mediastinal mass and multiple enlarged lymph nodes.

Interventions: Nephrotic syndrome secondary to a malignant mediastinal tumour was suspected; therefore, the patient underwent resection of the anterior mediastinal mass. Histopathological examination of the resected specimen showed lymphocytic proliferation without signs of malignancy. These findings were compatible with hyaline vascular type Castleman disease (CD), and with the associated multiple lymph nodes enlargement, the patient was initially diagnosed with multicenteric CD.

Outcomes: After resection of the whole tumour, all the clinical symptoms improved. However, after resection 6 months passed, the patient developed thrombocytopenia, anaemia, renal dysfunction, further enlargement of the residual lymph nodes, hepatosplenomegaly, and mild myelofibrosis. A diagnosis of TAFRO syndrome (TS) was eventually made. All symptoms improved with initial intravenous pulse steroid therapy followed by oral steroids. Histopathological examination of the renal biopsy samples showed findings resembling membranoproliferative glomerulonephritis (MPGN).

Lessons: In TS, all characteristic signs may not exist from the beginning. The association between TS and CD is not clear. When we compared our findings with previously published cases of TS and CD, we found that the renal pathology findings resembled MPGN in many cases of TS, while only a few cases showed amyloidosis. Recent results suggest that TS may be an independent disease from CD, and given the frequency of renal pathology findings, it may also have a different aetiology. To the best of our knowledge, this case report is rare to demonstrate the renal pathology in a patient with conventional TAFRO syndrome.
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http://dx.doi.org/10.1097/MD.0000000000011057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023668PMC
June 2018

Fascin as a Useful Marker for Identifying Neural Components in Immature Teratomas of Human Ovary and Those Derived From Murine Embryonic Stem Cells.

Int J Gynecol Pathol 2019 Jul;38(4):377-385

Tokyo Medical University (R.U.) Departments of Molecular Pathology (A.K., M.T., K.F., M.K.) Anatomic Pathology (T.N.), Tokyo Medical University Department of Diagnostic Pathology, NTT Medical Center Tokyo (H.H.), Tokyo, Japan.

Immature teratoma of the human ovary is a rare disease, and its diagnosis and grading are currently based on histologic evaluation of the presence and amount of immature neural components in the tumor. Despite the importance of tumor grading, immature neural components especially without rosette formation are difficult to identify, partly because useful biomarkers for them are not yet available. Toward this goal, we investigated 16 immature teratomas from human ovaries as well as 10 of those derived from murine embryonic stem cells transplanted into immunodeficient mice. Immunohistochemistry was performed for cytokeratin, glial fibrillary acidic protein, S100, and fascin. It was demonstrated that glial fibrillary acidic protein and S100 expression was not observed in the immature neural components of immature teratomas derived from both human ovary and embryonic stem cells, although their expression was detected in mature neural tissues. In contrast, fascin immunopositivity was clearly found in both mature and immature neural components regardless of rosette formation in immature teratomas derived from both human ovary and embryonic stem cells. Assessment of immature neural components by fascin immunostaining yielded the same or slightly increased quantity than quantification based on hematoxylin and eosin staining. These results suggest that fascin immunostaining is useful as a biomarker in correctly diagnosing and grading human immature teratomas. Further, fascin immunostaining may contribute to the development of regenerative medicine through accurate assessment of the maturation status of pluripotent stem cell-derived tumors transplanted into immunodeficient mice.
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http://dx.doi.org/10.1097/PGP.0000000000000528DOI Listing
July 2019