A Cerebral Embolism Caused by a Malignant Peripheral Nerve Sheath Tumor in a Patient with Neurofibromatosis Type 1.

A 31-year-old man with neurofibromatosis type 1 (NF-1) had undergone resection of a malignant peripheral nerve sheath tumor (MPNST) on the buttock 3 months previously. He subsequently underwent mechanical thrombectomy for a hyperacute left middle cerebral artery embolism. Histopathologically, the emboli comprised neurofilament-positive pleomorphic tumor cells with geographic necrosis and conspicuous mitosis and were identified as MPNST. The patient died of respiratory failure due to lung MPNST metastasis on day 15 of hospitalization. To our knowledge, this is the first report of a spontaneous cerebral embolism due to MPNST in a NF-1 patient.

A case of small bowel aneurysm hemorrhage with submucosal tumor-like findings.

A 51-year-old woman visited our hospital with the chief complaint of tarry stools. Contrast-enhanced abdominal computed tomography revealed leakage of contrast medium into the lumen of the small intestine. Subsequently, a double-balloon endoscopy was performed, which revealed a submucosal mass-like lesion in the jejunum. Although hemostasis was attempted with clips, complete hemostasis was difficult to achieve, and angiographic embolization was performed. Nevertheless, the anemia progressed, and a small bowel resection was performed. Histopathological examination led to a diagnosis of a ruptured submucosal aneurysm of the small intestine. Endoscopic hemostasis is often difficult to achieve for submucosal aneurysms in the intestine. The submucosal tumor-like finding observed on endoscopy in submucosal aneurysms is termed an "SMT-like sign" and is considered an important finding to diagnose aneurysms.

Can EUS-FNA cytology reliably classify gastric submucosal spindle cell tumors?

BACKGROUND: Cytological diagnosis using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for gastric submucosal spindle cell tumors, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas, is challenging because of their similar morphological characteristics. OBJECTIVE AND MATERIALS: To clarify the cytological differential points, we reviewed the EUS-FNA cytology specimens of GISTs (37 cases), leiomyomas (11 cases), and schwannomas (4 cases). METHOD: Twelve cytomorphological features were evaluated: lymphocytes, crushed nuclei, naked spindle nuclei, mast cell, length of the streaming arrangement, cellularity, nuclei at the cluster margin (nuclei located at the periphery of the cell cluster), peripheral feathering (loosely aggregated cells at the margin of a cell cluster tended to taper like feathers), metachromasia, wavy nuclei, fishhook-type nuclei, and anisonucleosis. RESULTS: Among these features, lymphocytes, naked spindle nuclei, length of the streaming arrangement, cellularity, nuclei at the cluster margins, peripheral feathering, and anisonucleosis were statistically significant for differentiation. Based on these findings, we developed an algorithm for cytodiagnosis. The algorithm was taught to four cytologists, and the interobserver agreement and correct diagnosis rates were compared before and after education, which showed a significant improvement. DISCUSSION: The histological types of gastric submucosal spindle cell tumors can be estimated using this algorithm for EUS-FNA cytology. Furthermore, this algorithm can be applied for cytological diagnosis at bedside during rapid on-site evaluation.

Immune-related dermatitis during combined treatment with pembrolizumab and axitinib in a patient with metastatic renal cell\x92carcinoma with stasis dermatitis.

INTRODUCTION: The combination of pembrolizumab and axitinib has recently been approved as a first-line treatment for previously untreated metastatic renal cell carcinoma. However, immune-related adverse events are not well known. CASE PRESENTATION: A 65-year-old male was diagnosed with renal cell carcinoma with metastases to the brain and lungs. The patient had a medical history of stasis dermatitis. During the combined treatment of pembrolizumab and axitinib, blisters appeared on the lower extremities. Skin biopsy revealed septal panniculitis, pustules, and perivascular lymphocytic and neutrophilic infiltration of the skin, and the patient was diagnosed with immune-related dermatitis. The dermatitis improved with oral prednisolone treatment. CONCLUSION: A case of immune-related dermatitis during combinatorial treatment with pembrolizumab and axitinib for renal cell carcinoma has been reported. Preexisting stasis dermatitis may have affected the onset and deterioration of immune-related dermatitis.

Pleural nodule with osteal protrusion anterior to the rib tubercle: a case report.

Pleural soft tissue density nodules with osteal protrusions are often detected at their characteristic site, the anterior portion of the rib tubercle. Herein, we report a pathologically proven case of this lesion. A 65-year-old man underwent surgery for primary lung cancer in the right middle lobe. Preoperative computed tomography showed a 10-mm pleural soft tissue density nodule with osteal protrusion anterior to the tubercle of the right sixth rib, and this lesion was concomitantly resected. Intraoperative findings showed that this pleural lesion originated from the parietal pleura and was pathologically diagnosed as a benign fibrous tissue. We can avoid unnecessary invasive examinations such as biopsies by recognizing these benign fibrous lesions.

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

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.

Cisplatin plus pemetrexed therapy and subsequent immune checkpoint inhibitor administration for malignant peritoneal mesothelioma without pleural lesions: Case report.

RATIONALE: Malignant peritoneal mesothelioma is a rare tumor with a poor prognosis and has no recommended therapy after first-line pemetrexed and platinum-based chemotherapy. Moreover, effects of immune checkpoint inhibitors on peritoneal mesothelioma remains to be elucidated. We herein report the case of a 75-year-old man with peritoneal mesothelioma treated with cisplatin plus pemetrexed and subsequent nivolumab. PATIENT CONCERNS: A 75-year-old man was referred to our hospital due to lower abdominal pain. DIAGNOSIS: Positron emission tomography-computed tomography (CT) showed the accumulation of fluorodeoxyglucose in an intraperitoneal mass. A histological examination of a laparoscopic biopsy specimen revealed malignant peritoneal mesothelioma. INTERVENTIONS: After 4 cycles of cisplatin plus pemetrexed and 13 subsequent cycles of pemetrexed maintenance therapy showed beneficial responses until CT revealed liver metastasis. Nivolumab was then administered as the second-line therapy. OUTCOMES: After 3 cycles of biweekly nivolumab administration, he developed severe abdominal distention. CT revealed an intraperitoneal mass growing much more rapidly than ever, indicating hyperprogressive disease after nivolumab treatment. He ultimately died 51 days after the initial nivolumab administration. LESSONS: To our knowledge, this is the first report of hyperprogressive disease in a case of peritoneal mesothelioma after nivolumab treatment. While immune checkpoint inhibitors may be promising therapeutic strategies for treating malignant peritoneal mesothelioma, careful monitoring must be practiced with their application.

A Novel Role of Interleukin 13 Receptor alpha2 in Perineural Invasion and its Association with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma.

Perineural invasion (PNI) is one of the major pathological characteristics of pancreatic ductal adeno-carcinoma (PDAC), which is mediated by invading cancer cells into nerve cells. Herein, we identify the overexpression of Interleukin-13 Receptor alpha2 (IL-13Rα2) in the PNI from 236 PDAC samples by studying its expression at the protein levels by immunohistochemistry (IHC) and the RNA level by in situ hybridization (ISH). We observe that ≥75% samples overexpressed IL-13Rα2 by IHC and ISH in grade 2 and 3 tumors, while ≥64% stage II and III tumors overexpressed IL-13Rα2 (≥2+). Interestingly, ≥36 % peripancreatic neural plexus (PL) and ≥70% nerve endings (Ne) among PNI in PDAC samples showed higher levels of IL-13Rα2 (≥2+). IL-13Rα2 +ve PL and Ne subjects survived significantly less than IL-13Rα2 -ve subjects, suggesting that IL-13Rα2 may have a unique role as a biomarker of PNI-aggressiveness. Importantly, IL-13Rα2 may be a therapeutic target for intervention, which might not only prolong patient survival but also help alleviate pain attributed to perineural invasion. Our study uncovers a novel role of IL-13Rα2 in PNI as a key factor of the disease severity, thus revealing a therapeutically targetable option for PDAC and to facilitate PNI-associated pain management.

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

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.

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

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.

Association Between Helicobacter pylori Infection and Short-segment/Long-segment Barrett's Esophagus in a Japanese Population: A Large Cross-Sectional Study.

GOAL: The goal of this study was to investigate the relationship between Helicobacter pylori (H. pylori) infection and short-segment and long-segment Barrett's esophagus (SSBE and LSBE). BACKGROUND: H. pylori infection is reported to be inversely associated with Barrett's esophagus (BE) in western countries. However, the impact of BE segment length on the association between BE and H. pylori infection has scarcely been investigated. MATERIALS AND METHODS: The study subjects were 41,065 asymptomatic Japanese individuals who took medical surveys between October 2010 and September 2017. Using this large database of healthy Japanese subjects, we investigated the association between H. pylori infection and SSBE/LSBE. We used multivariable logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among the study subjects, 36,615 were eligible for the analysis. H. pylori seropositivity was significantly associated with a lower rate of LSBE (OR: 0.42; 95% CI: 0.16-0.91) and a higher rate of SSBE (OR: 1.66; 95% CI: 1.56-1.78) after multivariate adjustment. In the subgroup analysis, H. pylori seropositivity was significantly associated with a high rate of SSBE in subjects without reflux esophagitis (RE) (OR: 1.73; 95% CI: 1.61-1.85). However, H. pylori seropositivity was not associated with SSBE in subjects with RE (OR: 1.07; 95% CI: 0.84-1.37). CONCLUSION: In a Japanese population, H. pylori infection was inversely associated with LSBE but significantly associated with SSBE only in subjects without RE. H. pylori may be a risk factor for SSBE, especially in individuals without RE.

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

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.

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

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.

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

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.

Intrahepatic Carcinosarcoma With Cholangiocarcinoma Elements and Prominent Bile Duct Spread.

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.

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

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.

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

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.

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

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.