杉本 曉彦

<jats:p>A 69-year-old man presented with hoarseness and cervical swelling. CT revealed a neck tumor and lymph node metastasis. Somatostatin receptor scintigraphy (SRS) showed mild lesion uptake. Intravenous tumor thrombus into the right internal jugular and vertebral vein was suggested by FDG-PET/CT and confirmed by Contrast-enhanced CT. Biopsy revealed squamous cell carcinoma (SCC). The tumor location and thrombosis suggested ectopic thymic origin. Immunostaining for markers CD117 and POU2F3 was positive, confirming ectopic thymic SCC. Chemotherapy was initiated, with tumor reduction after 6 months. This case highlights the usefulness of FDG-PET/CT suggestion of tumor thrombus and SRS accumulation in the diagnosis of ectopic thymic carcinoma.</jats:p>

Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell histiocytosis, characterized by the infiltration of disease-specific foamy histiocytes, polymorphic granulomas, and fibrosis. Although cardiovascular involvement is observed radiologically in approximately half of ECD patients, only a few reports have described its pathological features. We herein report the autopsy of an ECD patient with pulmonary, cardiovascular, and retroperitoneal involvement that may have caused his death. Autopsy revealed the pathological association of coronary and renal arterial stenosis with the BRAF^V600E gene mutation. BRAF mutations should be considered in patients with ECD, especially in those with arterial lesions.

<h4>Background</h4>Chondrosarcoma is typically a slow-growing tumor, and intratumoral hemorrhage is rare. Acute brainstem hemorrhage due to chondrosarcoma has rarely been reported.<h4>Observations</h4>A 77-year-old man presented with the sudden onset of headache and vomiting followed by a declining level of consciousness, progressive right hemiparesis, and left ophthalmoplegia. Magnetic resonance imaging showed pontine hemorrhage and a mass in the retroclival space compressing the brainstem. Emergency endoscopic endonasal surgery was performed. Intraoperative observation revealed that a hematoma was located in the pons and subdural space around the tumor mass, suggesting that the hematoma had likely been caused by the rupture of small vessels around the pons, not by intratumoral hemorrhage. The pathological diagnosis was chondrosarcoma. The patient recovered well and underwent radiotherapy.<h4>Lessons</h4>This report describes a case of sudden neurological deterioration due to hemorrhage in a patient with chondrosarcoma of the skull base. An emergency endoscopic endonasal approach for mass reduction and hematoma removal was effective in the acute setting. This approach revealed the suspected etiology of peritumoral hemorrhage, not intratumoral hemorrhage. https://thejns.org/doi/10.3171/CASE2460.

Radiation-induced angiosarcoma is a highly aggressive malignancy. We encountered a case of angiosarcoma arising in the bilateral breast seven years after partial mastectomy and the last radiation therapy. As recommended, wide resection with skin grafting was performed to ensure negative surgical margins. After surgery, taxane-based chemotherapy was administered. However, adjuvant chemotherapy was discontinued because of drug-induced institutional pneumonia. Eighteen months postoperatively, angiosarcoma recurred in subcutaneous, lymph nodes, lungs, and bones. The disease progressed too rapidly, and the patient died two months after recurrence.

<h4>Abstract</h4>A 70-year-old woman under amlodipine treatment for hypertension presented with a hemorrhagic mass in the mandibular gingiva. Imaging studies revealed high signal intensity in T2-weighted MRI and moderate 18F-FDG accumulation at the lesion's periphery. Although no malignancy was detected, the lesion continuously grew, prompting excision. Histopathological examination confirmed gingival hyperplasia attributed to amlodipine use. Drug-induced gingival hyperplasia typically presents as diffuse swelling; however, this lesion manifested as a polyp, posing diagnostic challenges. Reports on imaging findings for drug-induced gingival hyperplasia are limited. Understanding imaging patterns alongside clinical history aids in accurate diagnosis.

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal “stump”. Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal “tip” remnants.</jats:p> </jats:sec><jats:sec> <jats:title>Case presentation</jats:title> <jats:p>The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.</jats:p> </jats:sec>

<h4>Abstract</h4>A 64-year-old woman presented with chest pain while eating and was referred to our hospital. Physical examination revealed abdominal distension, tenderness, and lower-extremity edema. Imaging revealed a large gallbladder tumor infiltrating the liver, with ascites and pleural effusion. A biopsy confirmed a poorly differentiated adenocarcinoma with SMARCA4 deficiency (cT3N2M1, cStage IV). Chemotherapy was ineffective and led to tumor progression. The patient died 9 months later. Recently, attention has been paid to SMARCA4 deficiency, which is a genetic mutation found in tumors. Here, we report on poorly differentiated adenocarcinomas of the gallbladder based on imaging findings, including FDG PET.

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has a poor prognosis. Nelarabine has recently shown relatively good results in patients with relapsed or refractory T-ALL/LBL, but requires careful monitoring for neurological complications. A 50-year-old man with early recurrence of T-LBL after allogenic peripheral blood stem cell transplantation received nelarabine monotherapy and achieved complete remission after 1 cycle. He then received umbilical cord blood transplantation, and experienced sustained disturbance of consciousness. He later died of multiple organ failure, and autopsy suggested that nelarabine-induced leukoencephalopathy had caused the disturbance of consciousness. This case suggests that physicians should carefully monitor patients for neurological complications and consider imaging follow-up and consultation with a neurologist.

<h4>Abstract</h4>A 39-year-old man presented with a 1-month history of headaches. Imaging revealed a mass with extensive destruction. T2-weighted imaging displayed mixture of low and sponge-like high intensities and also dark area, with FDG PET/CT showing uneven but intense accumulation. Biopsy confirmed EWSR1 rearrangement, and hyalinizing clear cell carcinoma (HCCC) was diagnosed. HCCC, recently renamed from clear cell carcinoma in the fifth edition of the World Health Organization Classification of Head and Neck Tumors, is a rare tumor. This case describes the features of T2-weighted imaging and FDG PET patterns in HCCC, possibly contributing to their consideration in the differential diagnosis.

Malignant gastrointestinal neuroectodermal tumors (GNETs) are mesenchymal tumors that typically arise in the digestive tract and harbor EWSR1::ATF1 or EWSR1::CREB1 fusions. We report a case of primary retroperitoneal GNET in a 38-year-old woman who presented with a month-long fever with increased serum IL-6 level. A right retroperitoneal mass of 7 cm consisting of diffuse sheets of small cells with a high nuclear-to-cytoplasmic ratio and scattered osteoclast-like multinucleated giant cells was confirmed apart from the digestive tract. Peripheral lymphoid cuff and focal pseudoangiomatous spaces were present, reminiscent of angiomatoid fibrous histiocytoma. The tumor cells were positive for S100 protein and SOX10 and negative for melanocytic markers. Fluorescent in situ hybridization revealed EWSR1 and CREM gene rearrangements, consistent with EWSR1::CREM fusion, which has never been reported in GNET. The patient lives with recurrent lesions for 8 months. This case was associated with several unusual features and contributes to the evolving GNET concept.

<h4>Abstract</h4>A 47-year-old woman presented with a 2-month history of subcutaneous nodules, erythema, and fever. 18F-FDG PET images demonstrated inverted FDG uptake pattern corresponding to the subcutaneous lesion against lymph nodes. The specimen of the inguinal lesion showed massive infiltration of small lymphocytes in the adipose tissue with rimming adipocytes, whereas very few tumor cells infiltrated the lymph nodes. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) was diagnosed. SPTCL normally shows quite interesting distribution of tumor cells, that is, lymph node involvement is usually absent. Therefore, this case highlighted the importance of the inverted accumulation pattern on FDG PET to suspect SPTCL.

<h4>Abstract</h4>A 38-year-old man with von Hippel-Lindau (VHL) disease and a history of renal cell carcinoma presented with a 2-month history of recurrent epistaxis. MRI revealed a microcystic tumor in the left ethmoid sinus with strong contrast enhancement. 18F-FDG PET/CT showed FDG uptake (SUVmax, 4.2) in the lesion. Under the suspicion of renal cell carcinoma metastasis, the patient underwent 2 surgical resections. However, based on the morphological and immunohistochemical findings, the patient was finally diagnosed with a VHL-associated microcystic adenoma of the ethmoid sinus, which is an extremely rare tumor that occurs in VHL disease.

Intestinal amoebiasis is caused by Entamoeba histolytica (E. histolytica) and is characterised by cecal lesions, multiple lesions, aphthae, and multiple exudative erosions. Intestinal Behçet's disease (BD) is a chronic inflammatory disorder that is characterised by multiple ulcers. Although the aetiologies of these two bowel diseases are unrelated, they are difficult to distinguish because they present similarly with inflammation and ulcers, especially if evidence of specific pathogens is not detected. Herein, we report a case of intestinal amoebiasis in a patient with BD. The patient underwent colonoscopy four times before intestinal amoebiasis was diagnosed. As intestinal BD was initially suspected, she received high-dose glucocorticoid therapy, which exacerbated her condition. Following exacerbation, she underwent colonoscopy, and E. histolytica was revealed. Deliberate care should be taken to distinguish between intestinal amoebiasis and intestinal BD, as the appropriate treatments for these diseases are entirely different.

Decidualization of endometrial stromal cells and the presence of immunocompetent cells, including human mast cells, play important roles in the establishment of pregnancy. In the present study, the effects of decidualization of endometrial stromal cells on the function of decidual mast cells were elucidated. The in vitro assay revealed that decidualization of an endometrial stromal cell line, T HESCs, increased stem cell factor (SCF) mRNA expression. Decidualization of T HESCs enhanced the production of leukemia inhibitory factor (LIF), and the migration of LAD2 cells when co-cultured with T HESCs and LAD2 cells. In addition, decidualization of T HESCs enhanced cell migration in a human trophoblast cell line, HTR-8/SVneo, increased CD9 expression, a marker for extravillous trophoblast (EVT) differentiation, and decreased the secretion of β human chorionic gonadotropin (hCG), a marker for syncytiotrophoblast (ST) differentiation, when co-cultured with T HESCs, LAD2 cells, and HTR-8/SVneo cells, in a LIF-dependent manner. Histological samples from uterine pregnancies, including decidual stromal cells, showed increased SCF mRNA expression, mast cell numbers and LIF mRNA expression thereof compared with tubal pregnancy. SCF produced by decidual stromal cells enhanced the migration and LIF production of mast cells, and promoted the migration and differentiation of trophoblasts to increase the likelihood of successful human pregnancy.

The thymic medulla comprises various cell types, including tuft cells that are involved in innate immunity. We recently reported that in Western cohorts of patients, most thymic squamous cell carcinomas (TSQCCs), in contrast to thymomas, exhibit strong and extensive expression of tuft cell markers, including the tuft cell master regulator, POU2F3. On closer inspection of 94 thymomas that cover the full spectrum of thymoma histotypes, we now find by immunohistochemistry that approximately half of types A, AB, and B1 thymomas contain small numbers (< 10%) of cells expressing POU2F3, while most types B2 and B3 thymomas do not (p < 0.05). Further, in rarer types A and AB thymomas with adenoid growth pattern, POU2F3( +) cells formed aggregates and co-expressed KIT, as did the tumor cells in 100% (9/9) of TSQCCs expressing POU2F3. However, the expression of another tuft cell marker, L1CAM, still distinguished TSQCC from the spectrum of thymomas that were all L1CAM-negative. This study is the first to demonstrate the high frequency of POU2F3 expression in an Asian cohort of TSQCCs. The common occurrence of scattered POU2F3( +) cells in types A and AB thymomas hints at their variable degree of medullary differentiation and supports the historical hypothesis of the medullary nature of type A thymomas. Immunohistochemistry of L1CAM may be a valuable tool to differentiate TSQCCs from thymomas.

<h4>Background</h4>Craniopharyngioma (CP) often arises in the sellar and suprasellar areas; ectopic CP in the posterior fossa is rare. Familial adenomatous polyposis (FAP) is a genetic disorder involving the formation of numerous adenomatous polyps in the gastrointestinal tract, and it is associated with other extraintestinal manifestations.<h4>Observations</h4>The authors reported the case of a 63-year-old woman with FAP who presented with headache and harbored a growing mass in the fourth ventricle. Magnetic resonance imaging (MRI) findings revealed a well-circumscribed mass with high intensity on T1-weighted images and low intensity on T2-weighted images and exhibited no contrast enhancement. Gross total resection was performed and histopathology revealed an adamantinomatous CP (aCP). The authors also reviewed the previous reports of ectopic CP in the posterior fossa and found a high percentage of FAP cases among the ectopic CP group, thus suggesting a possible association between the two diseases.<h4>Lessons</h4>An ectopic CP may be reasonably included in the differential diagnosis in patients with FAP who present with well-circumscribed tumors in the posterior fossa.

<h4>Abstract</h4>Epstein-Barr virus-positive mucocutaneous ulcer is a newly recognized clinicopathological entity among mature B-cell neoplasms according to the 2016 revision of the World Health Organization diagnostic criteria. Here, we present FDG PET/CT images of 2 Epstein-Barr virus-positive mucocutaneous ulcer cases. Both cases shown in the images mimicked head and neck cancers, which are similar to carcinomas of the tonsil and gingiva, respectively, and both lesions showed intense FDG uptake on PET scan.

Angiomatous polyp is a benign, nonneoplastic nasal polyp that accounts for 4-5% of all inflammatory nasal polyps but is rarely reported in the literature. It can grow rapidly and exhibit an aggressive clinical behavior that can simulate malignant sinonasal tumor. We herein report a case of a 13-year-old boy with a rapidly growing angiomatous polyp in the nasal cavity. We had followed up the patient without significant changes for two years, but the tumor had rapidly grown in the last six months. At first, the rapid growth of the tumor and the bone erosion of the maxilla were suggestive of a malignant tumor. However, with preoperative magnetic resonance imaging (MRI) and [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography imaging findings, we established the corrective diagnosis of an angiomatous polyp. After the diagnostic imaging, we performed an endoscopic endonasal surgery and totally resected the tumor without unnecessary excessive surgery. Recognition of this disease that can mimic malignancy is important to avoid excessive surgery such as en bloc resection by craniofacial approach, and we believe that MRI findings can be helpful for the imaging diagnosis.

<h4>Abstract</h4>A 77-year-old man with parkinsonism was referred to the department of neurology for further examination. Cardiac 123I-MIBG scintigraphy unexpectedly showed strong uptake in the left shoulder, suggestive of MIBG-avid tumors including paraganglioma. MRI revealed multiple nodules suggestive of lymphoma. A biopsy was performed, which led to the pathological diagnosis of diffuse large B-cell lymphoma. Cardiac MIBG scintigraphy sometimes shows unexpected findings outside the mediastinum. In addition, lymphoma should also be added to the list of differential diagnoses for MIBG-positive tumors.

Multilocular thymic cyst (MTC) and germ cell tumors are common diseases that impact the mediastinum. Correctly diagnosing these diseases can be difficult because several other conditions can mimic them. We report a male patient with MTC associated with mediastinal seminoma. A needle biopsy of the mediastinal tumor revealed numerous epithelioid cell granulomas that mimicked sarcoidosis or mycobacterial infection. However, large atypical cells positive for Oct3/4 and KIT were noted between the granulomas; thus, we diagnosed the patient with mediastinal seminoma. The resected tumor, after chemotherapy, consisted of multiple cystic lesions, and a residual germ cell tumor was first considered. However, thymic medulla-specific elements, namely, POU2F3-positive thymic tuft cells and rhabdomyomatous myoid cells accompanying the epithelium, led to the correct diagnosis of MTC. Our case underscores the importance of recognizing the histological features associated with mediastinal seminoma and provides novel findings for MTC pathogenesis, namely, the presence of thymic tuft cells.

<h4>Objective</h4>To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients.<h4>Methods</h4>247 patients (LC, n = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups.<h4>Results</h4>ICI-P was identified in 26 patients in total (LC, n = 19; non-LC, n = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) (p = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) (p = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed (p = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows (p < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P.<h4>Conclusion</h4>ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients.<h4>Advances in knowledge</h4>In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.

Signaling lymphocytic activation molecule family member 8 (SLAMF8) / B-lymphocyte activator macrophage expressed/CD353 is a member of the CD2 family. SLAMF8 suppresses macrophage function but enhances the growth of neoplastic mast cells via SHP-2. In this study, we found that some anaplastic large cell lymphoma (ALCL) samples were immunohistochemically positive for SLAMF8. However, we found no significant differences between SLAMF8-positive and SLAMF8-negative ALCL samples with respect to age, gender, site, or prognosis. We also identified SLAMF8 expression in ALCL cell lines, Karpas299, and SU-DHL-1. SLAMF8 knockdown decreased the activation of SHP-2 and the growth of these cell lines, and increased the apoptosis of these cell lines. In addition, we observed the interaction between SLAMF8 and SHP-2 in these cell lines using the DuoLink in situ kit. Taken together, these results suggest that SLAMF8 may enhance the growth of ALCL via SHP-2 interaction.

The signalling lymphocytic activation molecule family member 8 (SLAMF8)/CD353 is a member of the CD2 family of proteins. Its ligand has not been identified. SLAMF8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF8 expression or function in human mastocytosis, which features oncogenic KIT-mediated proliferation of human mast cells. SLAMF8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF8 expression was also evident in the human mast cell lines, HMC1.2 (expressing oncogenic KIT) and LAD2 (expressing wild-type KIT) cells. SLAMF8 knock-down significantly reduced the KIT-mediated growth of HMC1.2 cells but not that of LAD2 cells. SLAMF8 knock-down HMC1.2 cells exhibited significant attenuation of SHP-2 activation and oncogenic KIT-mediated RAS-RAF-ERK signalling. An interaction between SLAMF8 and SHP-2 was confirmed in HMC1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS-RAF-ERK signalling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. SLAMF8 is a possible therapeutic target in human mastocytosis patients.

The involvement of mast cells in the establishment of pregnancy is unclear. Herein, we found that human mast cells are present in the decidual tissues of parous women and expressed a human-specific protein killer cell Ig-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen G expressed on human trophoblasts. In contrast, decreased numbers of decidual mast cells and reduced KIR2DL4 expression were observed in these cells of infertile women who had undergone long-term corticosteroid treatment. Co-culture of the human mast cell line, LAD2, and human trophoblast cell line, HTR-8/SVneo, accelerated the migration and tube formation of HTR-8/SVneo cells in a KIR2DL4-dependent manner. These observations suggest the possible involvement of human mast cells in the establishment of pregnancy via KIR2DL4 and that long-term corticosteroid treatment may cause infertility by influencing the phenotypes of decidual mast cells.