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Purpose: Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissues are rare mesenchymal neoplasms, some of which are malignant. However, their clinical and pathological characteristics remain unclear. This study was performed to investigate the clinical and pathological characteristics of PEComas in bone and soft tissues by leveraging information from the Japanese Musculoskeletal Oncology Group. Methods: Ten patients, including four male and six female patients with a median age of 49 years, were retrospectively reviewed. PEComas of the visceral organs, including the uterus and retroperitoneum, were excluded. Results: Nine tumors arose in the soft tissue and one in the bone, with a mean size of 9.3 cm. Four patients showed local recurrence or distant metastasis. The 1-year survival rate was 77%. Pathologically, eight tumors were classified as malignant and two as having uncertain malignancy potential. Half of the tumors showed high MIB-1 index values of >30%. Immunohistochemically, the melanocyte marker HMB45 was expressed in 90% cases, and muscle-specific markers were expressed only in 30–50% cases. Transcription factor binding to IGHM enhancer 3 (TFE3) expression was positive in 89% of the patients. Tumors with high expression of TFE3 were classified as PEComas with malignant potential according to Folpe’s classification. Conclusions: Bone and soft tissue PEComas may have a higher malignancy potential than other visceral PEComas and are more likely to develop as TFE3-rearranged PEComas.

Integrated PET/MRI with [18F]FDG is advantageous in that it enables simultaneous PET and MR imaging with higher soft-tissue contrast, multiplanar image acquisition, and functional imaging capability without using fat suppression and gadolinium-based contrast agents (GBCAs). The aims of this study were to demonstrate the feasibility of [18F]FDG PET/MRI for assessing the extent of the primary tumor (T) in oral tongue cancer (OTC) based on the 8th edition of American Joint Committee on Cancer (AJCC) cancer staging system, and to compare the diagnostic accuracy between [18F]FDG PET/MRI and contrast-enhanced MRI (ceMRI). 18 patients with biopsy-proven operable OTC underwent preoperative regional [18F]FDG PET/MRI and ceMRI within 2 weeks. For [18F]FDG PET/MRI, rainbow-colored PET images were overlaid on the corresponding MR images. Tumor size and the depth of invasion (DOI) were visually measured on [18F]FDG PET/MRI and ceMRI. The size, DOI, and clinical T stage were evaluated using the final surgical pathology as the reference. Of the 18 OTCs, one was not detected by ceMRI due to metal artifacts from an artificial denture, and another due to superficial type (pathological DOI = 0 mm). Tumor sizes measured by ceMRI and [18F]FDG PET/MRI had significant positive correlations with the pathological size (r = 0.80 and r = 0.90, respectively), and DOIs measured by ceMRI and [18F]FDG PET/MRI had significant positive correlations with the pathological DOI (r = 0.74 and r = 0.64, respectively). The means ± SD of size (mm) were 20.4 ± 9.1, 22.9 ± 10.9, and 26.2 ± 10.0, and those of DOI (mm) were 7.1 ± 2.5, 6.9 ± 2.2, and 5.8 ± 3.2 for ceMRI, [18F]FDG PET/MRI, and pathology, respectively. A significant difference was observed in tumor size between ceMRI and pathology (p

Tumors of the spinal cord and cauda equina show a wide spectrum of histology and require careful diagnosis and treatment. Primary intradural extramedullary Ewing sarcoma (IEES) is extremely rare, and initial imaging and clinical findings for this tumor mimic those of benign intradural spinal tumors. The present report describes a case of a 35-year-old woman who presented with IEES with meningeal seeding, and the literature on the management and clinical course of these tumors was reviewed. An examination revealed right-side leg dominant rapidly progressive hypoesthesia and motor deficits. MRI identified intradural tumors at the T12-L1 and L4-5 levels. Growth and an increase in the number of intradural tumors occurred over 3 weeks. Gadolinium-contrast T1-weighted MRI revealed diffusely enhanced signals for tumorous lesions with meningeal seeding in the cervical and thoracic spinal cord. Excision of a tumor at T12-L1 was performed to alleviate the symptoms and to make a histologic diagnosis. Microscopically, the tumor consisted of dense sheets of small round cells. Immunohistochemically, tumor cells showed intense and diffuse positive staining for CD99, ETS transcription factor ERG and Fli-1 proto-oncogene, ETS transcription factor (FLI1). The sequence analysis revealed the EWS RNA binding protein 1-FLI1 fusion transcript. The lesion was diagnosed as primary intradural ES. Adjuvant chemotherapy following radiotherapy for the whole spine was performed; however, multiple brain metastases were found at 10 months after diagnosis and the patient died of diffusely disseminated disease limited to the central nervous system without evidence of distant metastases at 16 months after the initial diagnosis. In a literature review of IEES cases, the 1- and 5-year overall survival rates were 79.8 and 26.6%, respectively, and the 1-, 2- and 5-year progression-free survival rates were 61.0, 52.3 and 10.9%, respectively. Therefore, primary IEES has a poor prognosis compared with ES of bone, and novel agents and treatment strategies are required.

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease involving the oral mucosa and skin. Both oral LP (OLP) and cutaneous LP (CLP) are histopathologically characterized by dense subepithelial lymphocyte infiltrates; however, the mechanisms underlying lymphocyte recruitment to sites of LP lesions are not fully understood. Here, we assessed the induction of peripheral lymph node addressin (PNAd)-expressing high endothelial venule (HEV)-like vessels in 19 OLP and 17 CLP cases. To do so, we performed immunohistochemical staining for PNAd and CD34, followed by quantitative analysis. We also conducted triple immunohistochemistry for PNAd and either CD3 and CD20 or CD4 and CD8 to identify the lymphocyte subset preferentially recruited via HEV-like vessels. PNAd-expressing HEV-like vessels were induced in and around lymphocyte aggregates in all cases of OLP and in 10 of 17 CLP cases, and these vessels were more frequently observed in OLP relative to CLP. Although the number of T-cells attached per HEV-like vessel exceeded the number of B-cells in both OLP and CLP, the number of CD4+ T-cells attached was greater than the number of CD8+ T-cells only in OLP. These findings combined suggest that PNAd-expressing HEV-like vessels play a more important role in the pathogenesis of OLP compared with CLP.

Salivary duct carcinoma (SDC) is a high-grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC.We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes.The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0-III cases.The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC.

The Japanese Society of Thyroid Pathology and the Japan Association of Endocrine Surgeons developed the eighth edition of the General Rules for the Description of Thyroid Cancer (GRDTC) in December 2019. This article describes the pathological diagnosis of the GRDTC, which has been improved through repeated revisions based on the experience of Japanese pathologists and translated into English to introduce the Japanese diagnostic standard to foreign countries. In this edition of the GRDTC, the histopathological classification and descriptions differ in some respects from those of the fourth edition of the World Health Organization (WHO) classification as revised in 2017. For example, the GRDTC does not adopt the concept of borderline lesions (FT-UMP, WDT-UMP, and NIFTP) of the WHO, taking into consideration the popular histological criteria accepted by Japanese pathologists. The cytological reporting system of the GRDTC was partly modified from the Bethesda system in 2015. It has an additional cyst fluid category separated from the unsatisfactory category that has been demonstrated to be useful in Japan. This translated edition makes it easy to submit Japanese clinicopathological studies of thyroid tumors in an international journal. We also wish to contribute to the improvement, standardization, and globalization of the pathological diagnosis of thyroid tumors.

A 75-year-old Japanese woman with a 20-year history of rheumatoid arthritis presented with symptomatic bilateral pleural effusion and lung and brain tumors. She had received methotrexate for five years and tacrolimus for one year. A brain biopsy specimen showed the pathological features of lymphoproliferative disease, but a bone marrow biopsy showed proliferation of plasma cells. She was finally diagnosed with coexistent lymphomatoid granulomatosis (LYG) of the brain and lung and multiple myeloma (MM) of the bone marrow and received chemotherapy for both. This report shows that immunodeficient patients are at risk of developing the unusual coexistence of LYG and MM.

BackgroundHeterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear.Case presentationAn 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-β1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7.ConclusionThis is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

Background Pancreatic hamartomas are rare entities and difficult to diagnose before resection. We report a case of resected pancreatic hamartoma and literature review of typical characteristics of the lesion. Case presentation A 78-year-old man presented with a mass in his pancreas, which was incidentally identified when he experienced pneumonia. No remarkable symptoms were observed, and laboratory tests showed no abnormalities, except a slight carcinoembryonic antigen elevation. Enhanced computed tomography and magnetic resonance imaging showed a well-demarcated solid mass with heterogeneous contrast that was 2 cm in size. A gradual enhancement pattern was also observed. The biopsy revealed no specific findings; therefore, surgical resection was necessitated to confirm the diagnosis. Histopathologically, ducts, acinar cells, and adipose cells without atypia were observed among abundant fibrous stroma, but islets of Langerhans and peripheral nerves were absent. An immunohistochemical examination demonstrated CD34 and c-kit positive staining in the stromal cells, S-100 positivity in the adipose cells, and a lack of elastic fibers in the duct walls. The lesion was diagnosed as a pancreatic hamartoma. Conclusion Asymptomatic pancreatic hamartomas can avoid resection. A careful consideration of imaging and appropriate immunohistochemistry of biopsy specimen may facilitate accurate diagnosis before resection. Therefore, sufficient recognition of the characteristics of pancreatic hamartomas is desirable.

Background and study aims Duplication cysts of the ileum are rare and present with non-specific clinical manifestations such as abdominal pain, vomiting, melena, and intussusception. Therefore, preoperative diagnosis is difficult. Here, we report a case of duplication cyst of the small intestine that was diagnosed preoperatively using double-balloon enteroscopy. A 19-year-old man presented with severe iron deficiency anemia, abdominal pain, and exertional dyspnea. Gastroscopy and colonoscopy revealed no remarkable findings. Abdominal computed tomography revealed a cystic structure in the ileum. Therefore, we performed double-balloon enteroscopy via the anal route. The intestinal tract was bifurcated, with one segment ending in a blind sac containing normal villi and an ulceration. Tc-99 m pertechnetate scintigraphy showed no accumulation in the lesion. Accordingly, we diagnosed a duplication cyst and suspected that this was the cause of severe anemia. Following small bowel resection with cyst excision and anastomosis, the anemia and presenting symptoms resolved. This report highlights the usefulness of double-balloon enteroscopy of the small intestine for preoperative diagnosis of the obscure gastrointestinal bleeding, including duplication cysts.

Macrophages in lungs can be classified into two subpopulations, alveolar macrophages (AMs) and interstitial macrophages (IMs), which reside in the alveolar and interstitial spaces, respectively. Accumulating evidence indicates the involvement of IMs in lung metastasis, but the roles of AMs in lung metastasis still remain elusive. An i.v. injection of a mouse hepatocellular carcinoma (HCC) cell line, BNL, caused lung metastasis foci with infiltration of AMs and IMs. Comprehensive determination of arachidonic acid metabolite levels revealed increases in leukotrienes and PGs in lungs in this metastasis model. A 5-lipoxygenase (LOX) inhibitor but not a cyclooxygenase inhibitor reduced the numbers of metastatic foci, particularly those of a larger size. A major 5-LOX metabolite, LTB4, augmented in vitro cell proliferation of human HCC cell lines as well as BNL cells. Moreover, in this lung metastasis course, AMs exhibited higher expression levels of the 5-LOX and LTB4 than IMs. Consistently, 5-LOX–expressing AMs increased in the lungs of human HCC patients with lung metastasis, compared with those without lung metastasis. Furthermore, intratracheal clodronate liposome injection selectively depleted AMs but not IMs, together with reduced LTB4 content and metastatic foci numbers in this lung metastasis process. Finally, IMs in mouse metastatic foci produced CCL2, thereby recruiting blood-borne, CCR2–expressing AMs into lungs. Thus, AMs can be recruited under the guidance of IM-derived CCL2 into metastatic lungs and can eventually contribute to the progression of lung metastasis by providing a potent arachidonic acid–derived tumor growth promoting mediator, LTB4.

Background Tumor-infiltrating lymphocytes (TILs) reportedly play a pivotal role in antitumor immunity against oral squamous cell carcinoma (OSCC); however, mechanisms governing TIL recruitment to OSCC tissues remain to be clarified. This study was undertaken to assess a potential association between TILs and high endothelial venule (HEV)-like vessels that express sialyl 6-sulfo Lewis X (LeX). Methods OSCC tissue sections (n=41) were subjected to immunohistochemistry for sialyl 6-sulfo LeX and CD34 to allow quantitation of HEV-like vessels. Triple immunohistochemistry for sialyl 6-sulfo LeX and either CD3 and CD20 or CD4 and CD8 was conducted to determine which lymphocyte subset is more closely associated with HEV-like vessels. Results HEV-like vessels expressing sialyl 6-sulfo LeX were detected in 27 of 41 (65.9%) OSCC cases, and these vessels were more frequently found in early disease (T1/T2 stages) compared with advanced (T3/T4) stages. The number of T cells attached to the inner surface of these HEV-like vessels was significantly greater than that of B cells, while the number of CD4+ helper T cells and CD8+ cytotoxic T cells did not differ significantly. Interestingly, sialyl 6-sulfo LeX was also expressed on the membrane of a fraction of OSCC cells, and CD8+ cytotoxic T cells were almost exclusively found attached to these carcinoma cells. Conclusions Sialyl 6-sulfo LeX is displayed not only on HEV-like vessels but also on OSCC cells and may potentially function in antitumor immunity against OSCC.

Rationale: Ossifying fibroma is benign fibro-osseous neoplasm. The authors report a case of ossifying fibroma in the mandibular angle suspected as metastasis of clear cell renal cell carcinoma. Patient concerns: A 74-year-old man presented to the primary hospital complaining of frequent urination. A tumor in the left kidney was detected via an abdominal computed tomography scan. The patient then visited the Department of Urology at our hospital. Diagnoses: According to whole-body imaging examinations, the patient was suspected of having renal cancer with mandibular metastasis. Also, a cystic lesion of the maxilla was revealed. Interventions: Left nephrectomy was performed by urologists, and the patient was diagnosed with clear cell renal cell carcinoma of the left kidney. Approximately 1 month later, resection with a safety margin of the mandibular lesion and removal of the maxillary lesion were performed by oral and maxillofacial surgeons. Outcomes: The patient was diagnosed with ossifying fibroma of the mandible and an odontogenic keratocyst of the maxilla via a histopathological examination. Eighteen months have passed since the operation without clinical and imaging findings associated with recurrence. Lessons: Ossifying fibroma in the mandibular angle of elderly patients is extremely rare. Surgeons should consider the possibility of metastasis when osteolytic lesions of the jaw are found in patients with cancer.

To consider the biologic behaviors of keratocystic odontogenic tumors (KCOTs) and ameloblastomas and dentigerous cysts.A 63-year-old Japanese man presented with swelling and discomfort in the left cheek during jaw movement. Examination revealed a multilocular lesion within the mandible extending from the left second premolar to the left mandibular ramus and coronoid process; the lesion contained a deviated impacted tooth. The tumor had expanded beyond the bone and was invading the masseter and medial pterygoid muscles. Marginal mandibulectomy with a free iliac bone graft was performed.No recurrence was observed during a 7-year follow-up.The histopathological diagnosis of the lesion showed it was a KCOT. These tumors usually grow within the bone, causing bone expansion. However, this tumor had expanded beyond the bone and invaded surrounding muscles. Thus, KCOTs can, in rare cases, manifest themselves as described here. Evaluating preoperative images and histopathological findings is important to determine the optimal treatment strategy.

Rationale Oral liposarcoma is an extremely rare lesion that is often clinically misdiagnosed as a benign lesion because of its asymptomatic and indolent clinical course. we report a case of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) of buccal mucosa, provisionally diagnosed as lipoma. Patient concerns A 97-year-old female was referred to dentistry and oral surgery department with an asymptomatic mass on the right buccal mucosa which had been present for an unknown period of time. Diagnosis Magnetic resonance imaging demonstrated a well-circumscribed lesion at the right buccal mucosa, and a lipoma was suspected. Interventions Surgical removal was performed, and a diagnosis of ALT/WDL was made. She and her family refused additional treatment due to her age. Outcomes At the 10 months follow-up, the patient remained free of disease. Lessons The indolent clinical course and small size of oral liposarcoma can lead to provisional clinical diagnosis of benign lesion.

Background and study aims: Primary neoplasms of the small intestine are relatively rare in all age groups, accounting for about 5 % of all gastrointestinal tumors 1 . Cavernous hemangiomas of the small intestine are also rare, can cause gastrointestinal bleeding, and are extremely difficult to diagnose preoperatively 2 . We present a patient who presented with melena and iron deficiency anemia, for whom wireless capsule endoscopy and single-balloon enteroscopy facilitated the diagnosis of cavernous hemangioma.

Renal metastasis at diagnosis with neuroblastoma is rare. We present a 14-month-old boy who was diagnosed with high-risk neuroblastoma with multiple metastases, including bilateral kidneys. He received five cycles of induction chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation. All of the lesions shrank, and magnetic resonance imaging indicated that some of the metastases had disappeared. However, there were residual masses in the bilateral kidneys, and histological examination revealed the presence of tumor cells. Therefore, the patient underwent unrelated cord blood stem cell transplantation, which involved killer-ligand incompatibility in the graft-versus-host direction, in addition to human leukocyte antigen C and DRB1 mismatches. Three months later, tumor progression occurred from the residual mass in the sacral canal and a new lesion in the pancreas. Although tumor progression could not be controlled by additional chemotherapy and local radiotherapy, the metastatic nodules in bilateral kidneys did not increase in size before his death. To the best of our knowledge, this is the first report of neuroblastoma with bilateral renal metastases in the English medical literature. In addition, this case suggests that the combination of chemotherapy and immunotherapy may inhibit the progression of the renal lesions under certain conditions.

Small cell carcinoma (SmCC) of the kidney is extremely rare. In this article, we present a review of SmCC of the kidney with the focus on clinical and pathobiological aspects. Macroscopically, this tumor often shows a bulky mass extensively replacing the renal parenchyma with vascular invasion and metastasis to lymph nodes. Histologically, the tumor is composed of small cells with scant cytoplasm, round to oval nuclei, finely granular chromatin and inconspicuous nucleoli. Rosette or tubular formation may be present. Immunohistochemically, neoplastic cells show variable positivity for neuron-specific enolase, chromogranin A, synaptophysin, CD57 (Leu7) and CD56. A dot-like staining pattern for cytokeratin may also be observed. An electron microscopic examination may identify electron-dense neurosecretory granules in the cytoplasm. As a therapeutic option, nephrectomy and systemic chemotherapy should be considered. However, despite multimodal therapy, most patients have a dismal outcome and die of widely metastatic disease within one to two years. As there are limited genetic data on SmCC of the kidney, a large series studying this will be needed in the future.

Case 74 y.o. male Chief Complaint Lower lip nodule Present History On July in XXXX, left hilar tumor was detected by chest computed tomography, and the patient was admitted to our hospital for scrutiny and treatment. It was diagnosed as stage IVa non-small cell lung cancer with undecidable histopathological subtype.Tumor proportion score of PD-L1 had shown 75%. Since Aug. in XXXX, Pembrolizumab was started. The tumor soon became smaller, so the therapy was thought to be effective. However, after 4 courses of those therapies, lower lip nodules appeared on October. Clinical Course Lower lip nodule had grown and formed a tumor in 1cm diameter, with scar in the central area and angiogenesis in the peripheral area. Lip tumor biopsy was performed at the end of October. In dermic layer, large cells with strain nucleus had increased. Abnormal cells showing CD3+, CD4+, CD8+, TIA-1+, CD30+, EBER(-), ISH(-), have indicated the possibility of T cell lymphoma. Since the association between immunotherapy and the lip nodule could not be denied, immunotherapy was ceased. In order to establish an accurate diagnosis of the lip tumor, resection of the nodule was carried out. At that time, the tumor had shrunk spontaneously, and the large abnormal cells had disappeared, which were detected in incisional biopsy. Considered with pathological findings and clinical course, primary skin lymphoproliferative diseases (LPD) had been diagnosed. As lung lesion was also enlarged simultaneously, Re-bronchoscopic exam revealed not LPDs but progression of cancer in the lung. Discussion LPD was confined in dermal layer of skin, occurred and disappeared in natural course. As the size of lip tumor decreased after cessation of immunotherapy, it was supposed that immunodeficiency due to the effect of Pembrolizumab might induce LPD.