Hepatic perivascular epithelioid cell tumors:The importance of preoperative diagnosis

Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the causes,properties and clinical manifestations of PEComas,we summarize the challenges and solutions in the diagnosis of PEComas.

Comprehensive clinicopathologic characteristics of intraabdominal neurogenic tumors:Single institution experience

BACKGROUND Neurogenic tumors are rare but represent an important consideration in the differential diagnosis of abdominal mesenchymal tumors.Reports on their incidence,pathological features and clinical characteristics are scarce.AIM To advance the overall knowledge on the histologic,immunohistochemical,clinical and radiologic characteristics of neurogenic tumors through this case series.METHODS An established database of a nationwide tertiary referral center,covering a 15-year period(2005 and 2020),was retrospectively re-evaluated.Diagnoses of neurogenic tumor cases were confirmed by two experts following review of the macroscopic,histological and immunohistochemical records along with findings from analysis of archived tissue sections for each included patient.Tissue microarrays were constructed for cases lacking necessary immunohistochemical studies.Clinical data and follow-up information were collected from the hospital records and the patients themselves,when available.RESULTS The study included 19 cases of intraabdominal neurogenic tumors,representing 12 women and 7 men, between 18 and 86 years of age (median: 51 years). Finalconfirmed diagnoses were 12 schwannomas, 2 diffuse submucosal neurofibromatoses,2 ganglioneuromas, 2 malignant peripheral sheath nerve tumors,and 1 mucosal Schwann cell hamartoma. Sizes of the tumors were variable, with amedian diameter of 4 cm;the two largest (> 10 cm) were schwannomas. Themajority of cases were asymptomatic at presentation, but the most frequentsymptom was abdominal pain. Gastrointestinal tract lesions were detected withendoscopy and extra-luminal lesions were detected with cross-sectional imaging.All cases were S100-positive and CD117-negative;most cases were negative fordesmin, epithelial membrane antigen, smooth muscle actin and CD34. In all but 5cases, the Ki67 proliferation index was ≤ 1%.CONCLUSION Re-evaluation of 19 cases of abdominal neurogenic tumors demonstrated considerablevariability in clinicopathologic characteristics depending on location,dimension and histological features.

Superficial Angiomyxoma of the Vulva: A Case Report

Superficial angiomyxoma is a rare benign mesenchymal tumor that mainly occurs in the genital region. We report the case of a 51-year-old woman with a painless vulvar mass, well circumscribed on ultrasound. On gross finding, it was a polypoid and bilobed mass, partially encapsulated. On histological examination, it was a proliferation of non-atypical spindle cells with an abundant, myxoid stroma and numerous medium-sized blood vessels. The diagnosis was superficial angiomyxoma. The clinical features do not often lead to the diagnosis of superficial vulvar angiomyxoma. It is based on histological examination and immunohistochemistry is helpful to differentiate it from other myxoid tumors.

Primary malignant liver mesenchymal tumor: A case report

Primary malignant liver mesenchymal tumor is a rare condition defined as a tumor with vascular, fibrous, adi-pose, and other mesenchymal tissue differentiation. We report a case of primary malignant liver mesenchymal tumor in a 51-year-old male with anemia, weight loss and hepatomegaly. Finally unconventional liver biopsy and histological manifestation led to the definitive diag-nosis.

Inflammatory myofibroblastic tumor of the distal common bile duct:Literature review with focus on pathological examination

Inflammatory myofibroblastic tumor(IMT)of the biliary tract is rare,and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features.Histologically,IMTs are(myo)fibroblastic neoplasms with a prominent inflammatory infiltrate.They are characterized by receptor tyrosine kinase gene rearrangements,most often involving an anaplastic lymphoma kinase(ALK)translocation.The final diagnosis of IMT depends on histopathology and immunohistochemical examination.In this manuscript,we provide a clinical and morphomolecular overview of IMT and the difficulties that may arise in using immunohistochemical and molecular techniques in diagnosing IMT.

Aggressive angiomyxoma of the epididymis: A case report

BACKGROUND Aggressive angiomyolipoma is an extremely rare benign mesenchymal tumor that was originally described as a locally recurrent mucinous spindle cell tumour.Agg-ressive angiomyolipoma originates from myofibroblasts,vascular smooth muscle cells,or fibroblasts,and displays various phenotypes of myofibroblasts and abnor-mal muscle arteries.Aggressive angiomyolipoma was first identified in 1983 and fewer than 50 male patients have been reported to date.It is an extremely rare mesenchymal tumour and often confused with other diseases.Patients with epididymal aggressive angiomyolipoma lack typical symptoms,most of which occur incidentally,although some patients may experience mild pain,discomfort,and swelling.Pain may be exacerbated by pressure from the mass.CASE SUMMARY A 66-year-old male was admitted to the hospital on January 14,2022 with chief complaint of swelling in the left scrotum for one year.There was no apparent cause for the swelling.The patient did not consult with any doctor or receive any treatment for the swelling.The enlarged scrotum increased in size gradually until it reached approximately the size of a goose egg,and was accompanied by discom-fort and swelling of the left cavity of the scrotum.The patient had no history of any testicular trauma,infection,or urinary tract infection.The patient urinated freely,1-2 times at night,without urgency,dysuria(painful urination),or haematuria.There was no significant family history of malignancy.The patient underwent excision of the enlarged tumour and the left epididymis under general anaes-thesia on January 18,2022.Twelve months of follow-up revealed no recurrence.The patient was satisfied with the treatment.CONCLUSION Aggressive angiomyolipoma is extremely rare clinically and often confused with other diseases.The pathogenesis of aggressive angiomyolipoma is unclear and the clinical presentation is mostly a painless enlarged mass.The diagnosis of aggressive angiomyolipoma requires a combination of medical history,preoperative imaging such as computed tomography and magnetic resonance imaging,cytological examination and preoperative and postoperative pathological biopsy.The preferred treatment is surgery,with the possibility of a new alternative treatment option after hormonal therapy.Aggressive angiomyolipoma should be considered in the differential diagnosis of parametrial tumors of the male genital area that present as clinically significant masses.The high recurrence rate of aggressive angiomyolipoma may be related to incomplete tumor resection,and patients with aggressive angiomyolipoma are advised to undergo annual postoperative follow-up and imaging for recurrence.

Adult-onset hypophosphatemic osteomalacia as a cause of widespread musculoskeletal pain:A retrospective case series of single center experience

BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations.AIM To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM.METHODS A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic(spine and musculoskeletal pain clinic)primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019.We enrolled patients with hypophosphatemia,high serum bone-specific alkaline phosphatase levels,and at least one imaging finding suggestive of OM.RESULTS Eight patients with adult-onset hypophosphatemic OM were included.The back was the most common site of pain.Proximal dominant symmetric muscle weakness was observed in more than half of the patients.Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns.Six patients were diagnosed with adefovir(ADV)-induced Fanconi syndrome,and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy,respectively.After phosphorus and vitamin D supplementation and treatment for the underlying etiologies,improvements in pain,muscle strength,and gait were observed in all patients.CONCLUSION Mechanical pain characteristics,hypophosphatemia,and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM.ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.

Gastric plexiform fibromyxoma:A case report

BACKGROUND Plexiform fibromyxoma(PF)is a rare mesenchymal tumor of the stomach.The clinical features of PF frequently include upper abdominal pain,abdominal discomfort,hematemesis,melena,pyloric obstruction and an upper abdominal mass.We herein report a case of PF resected by laparoscopic radical distal gastrectomy plus Roux-en-Y gastrojejunostomy.CASE SUMMARY The patient was admitted to hospital,due to a 1-wk history of an abdominal space-occupying lesion identified during a health examination.He underwent complete resection by laparoscopic radical distal gastrectomy plus Roux-en-Y gastrojejunostomy.During the operation,the tumor was located in the anterior wall of the gastric antrum(approximately 7 cm×6 cm×5.5 cm)and did not show evidence of invasion of the serosa.Histology showed that the tumor cells were oval fibroblast-like and spindle-shaped cells,with numerous thin-walled blood vessels and abundant myxoid stroma.Cellular atypia and mitosis were both rare.Immunohistochemistry showed that the tumor cells were immunoreactive for smooth muscle actin,S-100 and CD-10,but were negative for CD-117,CD-34,DOG-1,and ALK.In this case,S-100 was positive and no significant disease was observed during the follow-up period.CONCLUSION The fact that PF is a rare tumor with only a few cases in this region can lead to misdiagnosis of this entity and pose a real diagnostic challenge for general surgeons and pathologists when encountering such patients and differentiating PF from other primary tumors of gastric mesenchymal origin.Our report may help increase awareness of this rare,but important new disease entity.

Recent advances in the management of gastrointestinal stromal tumor

Gastrointestinal stromal tumor(GIST)is a rare but an important clinical entity seen in our clinical practice.It is the most common mesenchymal tumor of the gastrointestinal tract and most common malignancy of the small intestine.Although the exact prevalence of GIST is not known,the incidence of GIST has been increasing.GISTs arise from interstitial cells of Cajal.Most of the GISTs occur due to mutation in c-kit gene or platelet derived growth factor receptor alpha gene.15%of GISTs do not have these mutations and they are called wildtype GISTs.Almost all GISTs express KIT receptor tyrosine kinase.Histologically,GISTs look like spindle cell tumors most of the time but they can be epitheloid or mixed type.The median size of GISTs varies from 2.7 cm to 8.9 cm.Clinically,patients with small GISTs remain asymptomatic but as the GIST size increases,patients present with various symptoms depending on the location of the GIST.Most of GISTs are located in the stomach or small bowel.Diagnosis is suspected on imaging and endoscopic studies,and confirmed by tissue acquisition with immunohistochemical staining.The aggressiveness of GISTs depends on the size,mitotic index and location.Surgical resection is the treatment of choice.But various endoscopic modalities of resection are increasingly being tried.Tyrosine kinase inhibitors are extremely useful in the management of large GISTs,unresectable GISTs and metastatic GISTs.Treatment options for metastatic GISTs also include radiotherapy,chemotherapy,hepatic artery embolization,chemoembolization and radiofrequency ablation.

Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis

Objective:Osteosarcoma(OS)is an aggressive,highly metastatic,relatively drug-resistant bone tumor with poor long-term survival rates.The presence and persistence of circulating tumor cells(CTCs)in the peripheral blood are believed to be associated with treatment inefficiency and distant metastases.A blood-based CTC test is thus greatly needed for monitoring disease progression and predicting clinical outcomes.However,traditional methods cannot detect CTCs from tumors of mesenchymal origin such as OS,and research on CTC detection in mesenchymal tumors has been hindered for years.Methods:In this study,we developed a CTC test based on hexokinase 2,a metabolic function-associated marker,for the detection and surveillance of OS CTCs,and subsequently explored its clinical value.Twelve patients with OS were enrolled as the training cohort for serial CTC tests.Dynamic CTC counting,in combination with therapy evaluation and post-treatment follow-up,was used to establish a model for predicting post-chemotherapy evaluation and disease-free survival,and the model was further validated with a cohort of 8 patients with OS.Results:Two dynamic CTC number patterns were identified,and the resulting predictive model exhibited 92%consistency with the clinical outcomes.This model suggested that a single CTC test has similar predictive power to serial CTC analysis.In the validation cohort,the single CTC test exhibited 100%and 87.5%consistency with therapy response and disease-free survival,respectively.Conclusions:Our non-invasive test for detection and surveillance of CTCs enables accurate prediction of therapy efficiency and prognosis,and may be clinically valuable for avoiding inefficient therapy and prolonging survival.

A rare synchrony of adenocarcinoma of the ampulla with an ileal gastrointestinal stromal tumor: A case report

BACKGROUND This is a unique case of a patient who was found to have two extremely rare primary malignancies synchronously,i.e.,an ampullary adenocarcinoma arising from a high-grade dysplastic tubulovillous adenoma of the ampulla of Vater(TVAoA)with a high-grade ileal gastrointestinal stromal tumor(GIST).Based on a literature review and to the best of our knowledge,this is the first report of this synchronicity.Primary ampullary tumors are extremely rare,with an incidence of four cases per million population,which is approximately 0.0004%.Distal duodenal polyps are uncommon and have a preponderance of occurring around the ampulla of Vater.An adenoma of the ampulla(AoA)may occur sporadically or with a familial inheritance pattern,as in hereditary genetic polyposis syndrome such as familial adenomatous polyposis syndrome(FAPS).We report a case of a 77-year-old male who was admitted for painless obstructive jaundice with a 40-pound weight loss over a two-month period and who was subsequently diagnosed with two extremely rare primary malignancies,i.e.,an adenocarcinoma of the ampulla arising from a high-grade TVAoA and a high-grade ileal GIST found synch-ronously.CASE SUMMARY A 77-year-old male was admitted for generalized weakness with an associated weight loss of 40 pounds in the previous two months and was noted to have painless obstructive jaundice.The physical examination was benign except for bilateral scleral and palmar icterus.Lab results were significant for an obstructive pattern on liver enzymes.Serum lipase and carbohydrate antigen-19-9 levels were elevated.Computed tomography(CT)of the abdomen and pelvis and magnetic resonance cholangiopancreatography were consistent with a polypoid mass at the level of the common bile duct(CBD)and the ampulla of Vater with CBD dilatation.The same lesions were visualized with endoscopic retrograde cholangiopancreatography.Histopathology of endoscopic forceps biopsy showed TVAoA.Histopathology of the surgical specimen of the resected ampulla showed an adenocarcinoma arising from the TVAoA.Abdominal and pelvic CT also showed a coexisting heterogeneously enhancing,lobulated mass in the posterior pelvis originating from the ileum.The patient underwent ampullectomy and resection of the mass and ileo-ileal side-to-side anastomosis followed by chemoradiation.Histopathology of the resected mass confirmed it as a high-grade,spindle cell GIST.The patient is currently on imatinib,and a recent follow-up positron emission tomography(PET)scan showed a complete metabolic response.CONCLUSION This case is distinctive because the patient was diagnosed with two synchronous and extremely rare high-grade primary malignancies,i.e.,an ampullary adenocarcinoma arising from a highgrade dysplastic TVAoA with a high-grade ileal GIST.An AoA can occur sporadically and in a familial inheritance pattern in the setting of FAPS.We emphasize screening and surveillance colonoscopy when one encounters an AoA in upper endoscopy to check for FAPS.An AoA is a premalignant lesion,particularly in the setting of FAPS that carries a high risk of metamorphism to an ampullary adenocarcinoma.Final diagnosis should be based on a histopathologic study of the surgically resected ampullary specimen and not on endoscopic forceps biopsy.The diagnosis of AoA is usually incidental on upper endoscopy.However,patients can present with constitutional symptoms such as significant weight loss and obstructive symptoms such as painless jaundice,both of which occurred in our patient.Patient underwent ampullectomy with clear margins and ileal GIST resection.Patient is currently on imatinib adjuvant therapy and showed complete metabolic response on follow up PET scan.

Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats

Background Acute lung injury （ALl） and end-stage acute respiratory distress syndrome （ARDS） were among the most common causes of death in intensive care units. The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS. Recent studies had demonstrated the importance of mesenchymal stem cells （MSCs） in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury. Here, our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS. Methods Bone marrow derived MSCs were obtained from Sprague-Dawley （SD） rats and their differential potential was verified. ALl was induced in rats byoleic acid （OA）, and MSCs were transplanted intravenously. The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours, 24 hours and 48 hours after OA-injection. Results The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs. The concentration of tumor necrosis factor-a and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs, whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours, 24 hours and 48 hours after OA-challenge. Conclusions Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS. Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.