Advancing rare cancer research by MALDI mass spectrometry imaging: Applications, challenges, and future perspectives in sarcoma.

MALDI mass spectrometry imaging (MALDI imaging) uniquely advances cancer research, by measuring spatial distribution of endogenous and exogenous molecules directly from tissue sections. These molecular maps provide valuable insights into basic and translational cancer research, including tumor biology, tumor microenvironment, biomarker identification, drug treatment, and patient stratification. Despite its advantages, MALDI imaging is underutilized in studying rare cancers. Sarcomas, a group of malignant mesenchymal tumors, pose unique challenges in medical research due to their complex heterogeneity and low incidence, resulting in understudied subtypes with suboptimal management and outcomes. In this review, we explore the applicability of MALDI imaging in sarcoma research, showcasing its value in understanding this highly heterogeneous and challenging rare cancer. We summarize all MALDI imaging studies in sarcoma to date, highlight their impact on key research fields, including molecular signatures, cancer heterogeneity, and drug studies. We address specific challenges encountered when employing MALDI imaging for sarcomas, and propose solutions, such as using formalin-fixed paraffin-embedded tissues, and multiplexed experiments, and considerations for multi-site studies and digital data sharing practices. Through this review, we aim to spark collaboration between MALDI imaging researchers and clinical colleagues, to deploy the unique capabilities of MALDI imaging in the context of sarcoma.

Follicular Dendritic Cell Sarcomas: CT and MRI Findings in 20 Patients.

OBJECTIVE. The objective of this study was to assess the imaging features of follicular dendritic cell sarcoma (FDCS) on CT and MRI. MATERIALS AND METHODS. The clinical data and pretreatment findings of 20 patients with pathologically proven FDCS on CT (n = 15), MRI (n = 7), or both (n = 2) were analyzed retrospectively. Tumor location, number, size, morphology, attenuation or signal intensity, margin, presence of metastases, and contrast enhancement were evaluated. RESULTS. FDCS originated from lymph nodes (n = 6) or a variety of extranodal sites (n = 14). The tumors were typically solitary and well-circumscribed. Extranodal lesions (mostly in the abdomen or mediastinum with mean diameter, 11.8 cm) were larger than nodal lesions (mean diameter, 6.5 cm). Nodal-type cases presented with homogeneous masses on CT and MRI. However, on CT, all extranodal tumors (n = 12) showed heterogeneous attenuation, of which 91.7% (11/12) contained areas of lower attenuation because of internal necrosis and 50.0% (6/12) showed calcifications. On MRI, primary hepatic or splenic tumors (n = 3) also appeared as large heterogeneous masses. Seven patients (35.0%) had advanced-stage disease, and intraabdominal extranodal cases were more likely to have regional lymphadenopathy (n = 4) and distant metastases (n = 5). Hypervascularity was seen in 90.0% (18/20) of patients and progressive enhancement was seen in 11 (78.6%) of 14 tumors with multiphase imaging. CONCLUSION. FDCS is a rare, mostly solitary, well-delineated malignancy. A nodal-type FDCS typically presents as a small homogeneous mass, whereas an extranodal FDCS in the mediastinum or abdomen manifests as a large heterogeneous mass with internal necrosis and calcifications accompanied by regional lymphadenopathy. Hypervascularity and progressive enhancement can be seen in the majority of tumors.

Rare double orifice mitral valve malformation associated with bicuspid aortic valve in Turner syndrome: diagnosed by a series of novel three-dimensional echocardiography and literature review.

BACKGROUND: Patients with both double orifice mitral valve (DOMV) and bicuspid aortic valve (BAV) malformation are rare. Although DOMV or BAV can be detected in some genetic syndromes, it has not been reported to simultaneously appear in Turner syndrome (TS). TrueVue, TouchVue, and TrueVue Glass are the latest technologies in advanced three-dimensional echocardiography (3DE), which is an important information supplement to two-dimensional echocardiography (2DE) for the diagnosis of congenital cardiac malformations. Herein we report the novel use of the above-mentioned technologies in the diagnosis and evaluation of a rare, combined valve malformation. Meanwhile, we also reviewed the literature for cases involving both DOMV and BAV and their association with various genetic syndromes. CASE PRESENTATION: We present the case of a 5-year-old girl diagnosed with TS because of a developmental delay. DOMV and BAV were found through echocardiographic examination. Three-dimensional transthoracic echocardiography as well as a series of novel advanced techniques were applied to clearly display the spatial structure of all tiers of the mitral valve apparatus, aortic valve, and arch to facilitate an accurate diagnosis. CONCLUSIONS: This is the first case in which both DOMV and BAV were associated with TS. Innovative TrueVue and TrueVue Glass offer unprecedented photographic stereoscopic images, while TouchVue technology greatly improved the ultrasonic diagnostic workflow and the diagnostic performance of rare valve malformations by adding virtual light sources to display realistic light-shadow effects.

Enlarged uterine fibroid forming uterine diverticulum during pregnancy: a case report.

BACKGROUND: Although uterine fibroids are a common gynecologic neoplasm, uterine diverticulum accompanied by a uterine fibroid is unique. In addition, pregnancy complicated with uterine diverticulum is extremely rare. We experienced a case of a uterine fibroid that was associated with a uterine diverticulum that enlarged during pregnancy and puerperium. CASE PRESENTATION: A 25-year-old nulligravida woman had an abnormal uterine cavity surrounded by myomatous mass. After natural conception, the mass and pouch had enlarged during pregnancy. Six months after elective cesarean delivery, she underwent laparotomy because of abdominal pain caused by the myomatous mass and the fluid inside. The tumor was connected to the midline of the posterior wall of the normal uterus. The resected tumor was pathologically diagnosed as leiomyoma and diverticulum. CONCLUSIONS: Pregnancy can stimulate uterine fibroids to form uterine diverticula. Resection of the diverticulum and fibroid is a useful option for symptomatic patients with desired future fertility.

Added value of contrast-enhanced ultrasound (CEUS) in the diagnosis of primary retroperitoneal serous adenocarcinoma: a case report.

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is a rare malignant disease. Given the rarity of the disease, the imaging features of PRSA are unclear. Contrast-enhanced ultrasound (CEUS) also plays an important role in the evaluation of the differential diagnosis of retroperitoneal lesions. CASE PRESENTATION: We report the case of a 62-year-old woman of with increased CA125 levels for 1 year who was referred to our hospital. After conducting contrast-enhanced computed tomography and magnetic resonance imaging, the mass was misdiagnosed as a chocolate cyst. After transvaginal ultrasound (TUS) combined with CEUS, cystadenocarcinoma was considered as the initial diagnosis. Pathology results confirmed PRSA as the final diagnosis. CONCLUSIONS: CEUS features of PRSA are reported for the first time based on this case, potentially aiding in the differential diagnosis of this rare entity before surgery.

Imaging features and radiologic-pathologic correlations of inflammatory pseudotumor-like follicular dendritic cell sarcoma.

BACKGROUND: Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare tumor. This study aimed to reveal the radiological characteristics of IPT-like FDCS by radiologic-pathologic correlation. RESULTS: We analyzed two cases of IPT-like FDCS in the liver, nine in the spleen, and two in both the liver and spleen concomitantly. IPT-like FDCS presented as well-defined iso- or hypodense masses on unenhanced computed tomography (CT) images in both the liver and spleen. Hyperintensities on T1-weighted images and hypointensities on T2-weighted images with hypointense rings were characteristic features in splenic cases. "Halo signs" were observed in two out of three liver tumors. Hepatic lesions showed significant enhancement, whereas splenic lesions showed only mild enhancement. Delayed annular enhancement was observed in both liver and spleen cases. On ultrasonographic examination, IPT-like FDCS presented as hypoechoic lesions with enhancement similar to that observed on CT. Hyaline fibrous pseudocapsules, which correlated with the hypointensities on T2-weighted images, were microscopically observed at the tumor edge. IPT-like FDCS was characterized by an abundance of small blood vessels and capillaries. Capillaries were also found in the fibrous capsule of some IPT-like FDCSs, which may explain the delayed annular enhancement. CONCLUSIONS: The manifestations of IPT-like FDCS in the liver and spleen showed differences that warrant them to be approached differently during diagnosis. Characteristic radiological findings of IPT-like FDCS included different enhancement patterns between liver and spleen tumors and rim-like hypointensities on T2-weighted images, as well as annular enhancement on CT and magnetic resonance images. These imaging features correlated with tumor pathology.

The role of rare breast cancers in the false negative strain elastography results.

PURPOSE: Elastography was primarily used as an adjunctive method along with ultrasonography in differentiation between benign from malignant lesions. Occasionally, overlaps can occur which are caused by some rare invasive breast cancers. Our aim is to analyze the role of rare breast cancers in false negative strain elastography results and to assess the relation among false negative results and tumor size, lesion distance to skin, and tumor grade. METHODS: Patients with BI-RADS 5 category underwent strain elastography and core biopsy. All those with confirmed invasive breast cancer were included. For each rare breast cancer, four usual invasive breast cancer cases were taken as a control group. The cut-off value of strain ratio was considered as 2.3. The true positive and the false negative groups were compared in terms of histological type (rare carcinomas and the others) and the other parameters. Pearson Chi-square and Fisher's exact test were used for statistical analyses. P values < 0.05 were considered statistically significant. RESULTS: One hundred-thirteen patients were defined as true positive (70.6%), and 47 patients were defined as false negative (29.4%). Strain ratio values of the rare breast cancers were significantly lower than those of the other breast cancers (p = 0.012). There was no statistically significant difference between the groups with respect to tumor size, distance to skin, and tumor grade (p > 0.05). CONCLUSION: The rare breast cancers are an important cause of false negativity in elastographic evaluation of invasive breast cancers. The results should be interpreted in combination with grayscale US findings.

Hybrid Materials Based on Magnetic Iron Oxides with Benzothiazole Derivatives: A Plausible Potential Spectroscopy Probe.

Rare diseases affect a small part of the population, and the most affected are children. Because of the low availability of patients for testing, the pharmaceutical industry cannot develop drugs for the diagnosis of many of these orphan diseases. In this sense, the use of benzothiazole compounds that are highly selective and can act as spectroscopy probes, especially the compound 2-(4'-aminophenyl)benzothiazole (ABT), has been highlighted. This article reports the design of potential contrast agents based on ABT and iron to develop a new material with an efficient mechanism to raise the relaxation rate, facilitating diagnosis. The ABT/δ-FeOOH hybrid material was prepared by grafting (N-(4'-aminophenyl) benzothiazole-2-bromoacetamide) on the surface of the iron oxyhydroxide particles. FTIR spectra confirmed the material formations of the hybrid material ABT/δ-FeOOH. SEM analysis checked the covering of nanoflakes' surfaces in relation to the morphology of the samples. The theoretical calculations test a better binding mode of compound with iron oxyhydroxide. Theoretical findings show the radical capture mechanism in the stabilization of this new material. In this context, Fe3+ ions are an electron acceptor from the organic phase.

Thalassemia in the emergency department: special considerations for a rare disease.

Thalassemia is characterized by a defect in the synthesis of one or more of the globin subunits of hemoglobin. This defect results in imbalance in the α/ß-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. With advances in diagnosis, treatment, and transfusion support, the prognosis of patients with thalassemia has improved over the past few decades. An increasing number of patients with thalassemia is living with long-term complications, including cardiomyopathy, chronic liver disease, endocrinopathy, and infections. In this paper, we review common complications that bring the patient with thalassemia to urgent or emergent medical attention. We also discuss the aspects of emergency care that are most relevant while caring for the patient with thalassemia in the emergency department.

TKA in the treatment of bilateral dysplasia epiphysealis hemimelica (Trevor's Disease) of the knee in a 50-year-old man: a case report.

BACKGROUND: Dysplasia epiphysealis hemimelica (DEH), also known as Trevor's disease, is a rare skeletal developmental disorder affecting the epiphyses in pediatric patients. DEH is characterized by an asymmetric osteochondral overgrowth arising from either the medial or lateral portion of an epiphysis and usually occurs in the joints of lower limbs, most commonly in the knees and ankles. However, bilateral involvement in an adult is extremely rare, and total knee arthroplasty (TKA) for a patient with DEH has been reported only once before. CASE PRESENTATION: Here, we present a case of bilateral DEH of the knees that caused varus deformity and dysfunction of the lower limbs in a 50-year-old man. TKA was performed for treatment, and the patient had satisfactory function with no angular knee deformity and a normal range of motion after 1 year of follow-up. CONCLUSIONS: The patient in this case exhibited its specific clinical and radiological features of late-term DEH and TKA was proved to be an appropriate procedure for treating the severe deformity caused by this rare disease.

Successful use of hyperbaric oxygen therapy for limb salvage of acute limb ischemia as a complication of acute carbon monoxide poisoning.

Acute limb ischemia (ALI) as a complication of acute carbon monoxide (CO) poisoning is rare. Several reports have utilized hyperbaric oxygen therapy (HBO2) as an adjunctive therapy for peripheral arterial diseases. However, no study has yet described the use of HBO2 for ALI precipitated by CO poisoning. Herein we report successful limb salvage achieved with adjunctive HBO2 and conventional therapies in a patient with CO-induced ALI. A 69-year-old man was admitted with acute CO poisoning; ALI of both lower extremities occurred on hospitalization day 3. Pre-existing risk factors for ALI other than CO were not definite. After conventional treatments including catheter-directed thrombolysis and endovascular thrombectomy, the right-side lesion remained and a left-side lesion was newly developed. In addition to prior therapies, 47 sessions of serial HBO2 were administered as adjunctive therapy, resulting in limb salvage. Acute CO poisoning can cause ALI as a rare complication. HBO2 may be utilized as an adjunctive treatment in ALI.

Identification of extremely rare mitochondrial disorders by whole exome sequencing.

Whole exome sequencing (WES) is an effective tool for the genetic diagnosis of mitochondrial disorders due to various nuclear genetic defects. In this study, three patients affected by extremely rare mitochondrial disorders caused by nuclear genetic defects are described. The medical records of each patient were reviewed to obtain clinical symptoms, results of biochemical and imaging studies, and muscle biopsies. WES and massive parallel sequencing of whole mtDNA were performed for each patient. The oxygen consumption rate (OCR) and complex activity I and IV was measured. Patients 1 and 2 had exhibited global developmental delay and seizure since early infancy. Blood lactate, the lactate-to-pyruvate ratio, and urinary excretion of Krebs cycle intermediates were markedly elevated. Patient 1 also was noted for ophthalmoplegia. Patient 2 had left ventricular hypertrophy and ataxia. Patient 3 developed dysarthria, gait disturbance, and right-side weakness at age 29. Brain magnetic resonance imaging demonstrated abnormal signal intensity involving the bilateral thalami, midbrain, or pons. Based on WES, patient 1 had p.Glu415Gly and p.Arg484Trp variants in MTO1. In patient 2, p.Gln111ThrfsTer5 and RNA mis-splicing were identified in TSFM. Patient 3 carried p.Met151Thr and p.Met246Lys variants in AARS2. Skin fibroblasts of three patients exhibited decreased OCRs and complex 1 activity, and mitochondrial DNA was normal. These results demonstrate the utility of WES for identifying the genetic cause of extremely rare mitochondrial disorders, which has implications for genetic counseling.

Multiple intraneural glomus tumors in different digital nerve fascicles.

BACKGROUND: Glomus tumors in the digital nerve are extremely rare. Multiple intraneural glomus tumors in different digital nerve fascicles have not been previously reported. CASE PRESENTATION: We report the case of a 54-year-old male with a 1-year history of progressive numbness of the middle finger with point tenderness at the level of the middle phalanx. Surgical incision revealed the presence of two glomus tumors within different fascicles of the ulnar digital nerve of the middle finger. One tumor was excised along with surrounding fascicle, the other was removed leaving the fascicle intact. Subsequently, the patient regained function of the finger and no tumors have recurred. CONCLUSIONS: Patients and physicians should be aware of the properties of intraneural glomus tumors so that early diagnosis and treatment can be sought.

Osteomyelitis of the pubic symphysis caused by methicillin-resistant Staphylococcus aureus after vaginal delivery: a case report and literature review.

BACKGROUND: Osteomyelitis of the pubic symphysis is a rare cause of pelvic pain after delivery, mainly caused by Staphylococcus aureus and Pseudomonas aeruginosa. The clinical context is the same as the more common diastasis of the pubic bone, but the presence of intense local pain in association with fever should prompt further clinical work-up based on blood chemistry, microbiology and diagnostic imaging. We report the first case of methicillin-resistant Staphylococcus aureus osteomyelitis of the pubic symphysis occuring after the delivery. CASE PRESENTATION: A 39-year-old woman developed pain over the pubic bone 12 h after the delivery. After 72 h fever rose and laboratory examination showed elevation of C-reactive protein and procalcitonin levels. Pelvic x-rays and magnetic resonance showed pubic diastasis, joint effusion, tiny irregularities of articular surfaces and, severe bone edema. The patient was started on broad spectrum intravenous (IV) antibiotics (piperacillin-tazobactam) and then replaced to IV vancomycin and oral levofloxacin based on antibiogram result. She was then discharged with oral antibiotic therapy and fully recovered. CONCLUSIONS: Due to the rarity of this disease, we compared our experience with the other cases of osteomyelitis of pubic symphysis occurring in peri-postpartum reported in the literature. The course of osteomyelitis was favourable in all patients, and only in one case an additional orthopedic procedure for symphysis fixation was necessary. Knowledge of this rare condition is important to enable prompt diagnosis and treatment.

Solitary fibrous tumor of the scrotum: a case report and review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare soft tissue tumor originally reported in the pleura. Although it has been reported in various extra-pleural sites, the occurrence of SFT in the scrotum is extremely rare. Herein, we present a 48-year-old man who had scrotal SFT. There are very few reported cases of genitourinary SFTs, this is only the fifth report of SFT of the scrotum in the English medical literature. CASE PRESENTATION: In this study, we report on a 48-year-old man who presented with a 5 × 8 cm scrotal mass between his testes. Physical examination revealed a 4.7 × 8.5 cm lobulated tumor mass located between his testicles. Surgical excision of the tumor with scrotal approach was done and pathology reported a SFT. The patient was alive without tumor recurrence or distant metastasis during ongoing follow-up for 9 months post-operatively.. CONCLUSION: Scrotal SFTs are very rare and only five cases have been reported in English literature to date. Treatment often involves surgical resection, and a definite diagnosis is made with the help of immunohistochemistry. The current general consensus for the management of SFTs is long-term follow-up after surgical excision of the tumor.

Surgery following Extracorporeal Cardiopulmonary Resuscitation in a Patient with an Extracardiac Rupture of Valsalva Sinus Aneurysm.

The rupture of sinus of Valsalva aneurysm (SVA) into the pericardial cavity is extremely rare and fatal. A 52-year-old man presented with an abrupt onset of chest pain and dizziness. An echocardiography and a computed tomographic angiography revealed a giant aneurysm of the noncoronary sinus (NCS) (maximum, 70 mm) and pericardial effusion in favor of tamponade with a moderate degree of aortic insufficiency. On the way to the operating room, he suffered cardiac arrest, and extracorporeal cardiopulmonary resuscitation (ECPR) was initiated immediately. While he was prepared for surgery, the patient was supported by extracorporeal life support (ECLS) until cardiopulmonary bypass (CPB) was initiated. The sinus defect was reconstructed using a Dacron patch, followed by resection of the aneurysm. ECLS and CPB were discontinued successfully in the operating room. This study reports a case of an extracardiac rupture of SVA and the successful completion of surgery following ECPR.

A rare heterotopic gastric mucosa appearing between the muscularis mucosae and submucosa.

To the best of our knowledge, this is the first report of ectopic gastric mucosa appearing between muscularis mucosae and submucosa, at esophagogastric junction. Currently there are two theories explaining the mechanism. The most widely accepted one is that Ectopic gastric mucosa is an embryological remnant, and an alternative theory is abnormal proliferation under inflammation1.Although we don't have many evidences to clarify this case into specific mechanism mentioned above, Nomura et reported two cases of Adenocarcinoma of the cervical esophagus arising from ectopic gastric mucosa, Completely resected by ESD with no signs of recurrence2. Therefore, In this present case, the lesion was successfully managed with ESD. The symptoms were released after the operation and the patient remained well during a year follow-up. Long-term follow-up is recommended in case of recurrence or gastric cancer.

Primary colon mantle lymphoma: a misleading macroscopic appearance!

Mantle cell lymphoma (MCL) of the colon is a rare entity, usually presenting as lymphomatous polyposis. We report the case of a 43-year-old male with an unusual colonic MCL in the form of a single exophytic and ulcerous lesion with necrotic areas associated with an ileo-cecal intussusception. The endoscopic appearance suggested adenocarcinoma. However, the diagnosis was made by histology and immunohistochemistry studies of the endoscopic biopsies.

Limited Dorsal Myeloschisis with and without Type I Split Cord Malformation: Report of 3 Cases and Surgical Nuances.

Limited dorsal myeloschisis (LDM) is a rare form of spina bifida which is characterized by a fibroneural stalk between the inner part of the skin and the spinal cord. It may be associated with split cord malformation (SCM). Diagnosis and management of this complex malformation is challenging. We presented 3 different cases of LDM. Two of them were associated with Type I SCM and the other had no associated malformation. All of them were evaluated radiologically just after the birth and underwent surgical treatment under intraoperative neuromonitoring. They discharged without any complication. Newborns with spinal cystic lesions should be carefully evaluated for spinal malformations after the birth and treated surgically as soon as possible in order to prevent neurological and urological complications secondary to tethered cord syndrome. Surgical technique in LDM-SCM patients is quite different than the patients with solitary LDM.

An Atypical Case of Idiopathic Pulmonary Fibrosis in a Patient from Africa.

A 39 years old African man presented with fatigue, loss of weight and night sweats; radiology showed a possible usual interstitial pneumonia pattern. The patient missed follow-up visits, and presented again after 3 years with productive cough and general illness. Pulmonary function tests showed a decline of FVC compared to a previous investigation. The CT scans showed progression of the interstitial lung disease, and a multidisciplinary conference recommended to proceed with a surgical lung biopsy. Histopathology showed an atypical pattern, with bronchiolar metaplasia. A new multidisciplinary conference made a diagnosis of IPF, and the patient was treated with antifibrotic drugs with a good effect, reaching stability of lung function. This case report highlights the need to improve knowledge and to better characterize rare pulmonary diseases, and especially IPF, among African patients.