Pazopanib in Patients with Osteosarcoma Metastatic to the Lung: Phase 2 Study Results and the Lessons for Tumor Measurement

Background. This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable, pulmonary metastatic osteosarcoma. Patients and Methods. Patients with pulmonary metastatic osteosarcoma unresponsive to chemotherapy were eligible. Patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28-day cycles. Tumor responses were evaluated by local radiology assessment 1 month prior to and after initiation of treatment to calculate tumor doubling time and after every even numbered cycle. The primary endpoints were progression-free survival at 4 months, concomitant with a demonstrated 30% increase in tumor doubling time relative to the pretreatment growth rate. Results. 12 patients (7 female) were enrolled. The study was terminated prematurely due to withdrawal of financial support by the sponsor. 8 subjects were eligible for the primary analysis, whereas 4 patients were in a predefined exploratory “slow-growing” cohort. In the “fast-growing” cohort, 3 of the 8 patients (37.5%) eligible for first-stage analysis were deemed “success” by the preplanned criteria, adequate to proceed to second-stage accrual. In addition, 1 of the 4 patients in the “slow-growing” cohort experienced a partial remission. Grade 1-2 diarrhea was the most common adverse event, and grade 3 events were infrequent. Conclusion. This study illustrates a novel method of demonstrating positive drug activity in osteosarcoma by increasing tumor doubling time, and this is further supported by a partial response in a patient with “slow-growing” disease. This trial is registered with NCT01759303.

Rare Case of Gastric Schwannoma Simulating Gastrointestinal Stromal Tumour-A Case Report

Gastric schwannoma (GS) is a rare, benign, slow-growing neoplasm representing 0.2% of all gastric tumors. We report a rare case of Gastric schwannoma in a 56 year old woman who presented with abdominal discomfort and vomiting since few years. Contrast enhanced Computed Tomography showed a well-defined homogeneously attenuating lesion with homogenous enhancement. Wedge gastrectomy was done with a possible diagnosis of Gastrointestinal stromal tumor, but was confirmed to have Gastric schwannoma on histopathology showing spindle cells with peripheral cuff of lymphoid aggregates and S-100 protein positivity on immunohistochemistry. Gastric schwannoma should be included in the differential diagnosis of a gastric intramural or exophytic mass when Computed Tomography shows a well-defined homogeneously attenuating lesion with progressively increasing homogenous enhancement without hemorrhage, necrosis, and degeneration.

Intractable Trigeminal Neuralgia Secondary to Osteoma of the Clivus: A Case Report and Literature Review

Skull base osteomas (SBOs) are benign tumors that are frequently detected on radiographic images by coincidence. They are known for being slow-growing tumors and rarely symptomatic. The therapeutic approach for SBOs can differ substantially. Depending on the symptoms, size, and location of the tumor, this can range from serial observation to vigorous surgical extirpation. Clival osteoma is extremely rare. We report a case of clival osteoma, causing intractable trigeminal neuralgia due to the pressure effect on the trigeminal nerve at Meckel's cave. We also provide a review of pertinent literature. A 37-year-old woman presented with intractable trigeminal neuralgia. Cranial magnetic resonance imaging (MRI) demonstrated a large, lobulated, extra-axial lesion involving the right cerebellopontine angle and epicentering the clivus. Pathologically, the specimen was proven to be osteoma. The patient reported complete symptom resolution over a 4-year follow-up period. To the best of the authors' knowledge, this is the first clinical case of intractable trigeminal neuralgia due to clival osteoma.

Curious case of Retrosternal Colloid Goitre

Background: Retrosternal goitre is considered to be a rare entity. It is a slow growing enlargement of the thyroid gland which remains asymptomatic for many years. Symptoms are mainly due to compression of airways and oesophagus. Surgical management with the removal of the involved lobe is considered sufficient. Summary: Here we report a case of a 33 yrs. old lady who presented to us with complaints of neck pain, facial flushing, difficulty in breathing and vague body ache. Clinical examination was within normal limits. The patient was referred to orthopedician for further evaluation. MRI cervical spine was done which was suggestive of large swelling in left lobe of thyroid with retrosternal extension causing deviation of trachea to opposite side. FNAC was done which was inconclusive. The involved lobe was removed surgically with frozen section suggestive of Colloid goitre. Conclusion: Retrosternal goitre are slow growing enlargement of thyroid gland which may present with vague symptoms, best managed surgically often followed relief from the symptoms post-surgery.

Toxoplasma ceramide synthases: a curious case of gene duplication, divergence and key functionality

Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause foetal damage and abortion in both animals and humans. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localisation and analyses of the Toxoplasma ceramide synthases Tg CerS1 and Tg CerS2 and, using a conditional gene regulation approach, establish their roles in pathogenicity and parasite fitness. Interestingly, we observed that whilst Tg CerS1 was a fully functional orthologue of the yeast Lag1p capable of catalysing the conversion of sphinganine to ceramide, in contrast Tg CerS2 was catalytically inactive. Furthermore, genomic deletion of Tg CerS1 using CRISPR/Cas-9 led to viable but slow growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of Tg CerS2 was only accessible utilising the rapamycin-inducible Cre recombinase system. Surprisingly, the results demonstrated that this ‘pseudo’ ceramide synthase, Tg CerS2, has an even greater role in parasite fitness than its catalytically active orthologue (Tg CerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in Toxoplasma and other Apicomplexa arose through gene duplication. However, in the Apicomplexa the duplicated copy subsequently evolved into a non-functional ‘pseudo’ ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites, a feature that could potentially be exploited in the development of new antiprotozoals.

Patterned microfluidic devices for rapid screening of metal–organic frameworks yield insights into polymorphism and non-monotonic growth

Illustrated is a continuous-flow microfluidic device with patterned surface to induce faster nucleation of metal–organic frameworks (MOFs) and other slow-growing crystals, where the cyclonic flow allows trapping of crystals to grow them under controlled conditions.

Giant malignant Chondroid Syringoma: Case Report and Literature Review

Chondroitin syringoma, also known as cutaneous mixed tumor, is a rare type of sweat gland tumor, accounting for 0.01% to 0.1% of all primary tumors of the skin. The malignant form is extremely rare, with 41 cases described so far. It predominates in the trunk and distal extremities and affects women more frequently, with a 3: 2 rate 6,7. Patients may reach the health service with large lesions due to the fact of being slow-growing lesions and have a high rate of recurrence, requiring surgical treatment that may lead to extensive defects making complex reconstructions necessary. We present a case of malignant chondroid syringoma in an 80 years old male patient, with 29 years of evolution and unusual size. A reconstruction was performed with a muscular dorsal flap of the latissimus dorsi with good aesthetic and functional results, with no signs of recurrence after 8 months of follow-up. It is concluded that because it is a late diagnosis neoplasia, the surgical treatment ends up generating expressive defects. There for musculocutaneous should be considered as an option for reconstruction, aiming optimal functional and aesthetic restoration.

Myopericytoma of the Parotid and Molecular Profiling: Report of a Rare Case and Review of the Literature

Myopericytomas are uncommon tumors defined by their round to spindle shaped cells often arranged in a concentric pattern of perivascular growth. They are typically well-circumscribed, nodular, slow-growing lesions that occur in the soft tissue of the extremities. Here, we present a 30-year-old female with a 2.4 cm myopericytoma occurring in the deep lobe of the parotid gland. The diagnosis was made with detailed histopathologic and immunohistochemical findings and positive identification of the specific mutation for PDGFRβ p.Asp666Lys by next generation sequencing (NGS). This is the first case report of a parotid myopericytoma with a genetic testing that shows a particular mutation that has been linked to myopericytomatosis.

Clear Cell Odontogenic Carcinoma: A Rare Case Report

Clear Cell Odontogenic Carcinoma (CCOC) is a slow-growing, locally invasive odontogenic tumor affecting the jaws. It usually has confusing clinical characteristics, radiographical and histological features, making its recognition more challenging. In (2005), the WHO has reclassified CCOC as a malignant odontogenic tumor due to its aggressive behavior. This case report is about a woman who aged 42 years old, experienced swelling of the lower jaw and complained of paresthesia of the lips for two years. Radiographic findings showed an extensive, large, multilocular radiolucency lesion associated with scalloping, non-sclerotic border, and crossing the midline of the mandible. Histopathologically, the high-power view illustrated lobules of clear epithelial cells with clear cytoplasm. A review of English literature in PubMed Medline revealed few similar cases of CCOC affecting the mandible. The definitive diagnosis was consistent with CCOC; therefore, the patient was admitted to the hospital and surgical resection of the mandibular tumor was performed under general anesthesia. Long-term follow-up visits showed no signs of recurrence or post-surgical complications. We explain the signs and symptoms of CCOC such as symptomatic or asymptomatic jaw swelling, teeth loosening, displacement and mobility of teeth, and thinning of the mandible. Also, differential diagnosis and the nature of CCOC under the microscope were discussed and explained. The presentation of clear cell tumors is challenging, and it needs a meticulous investigation to determine the type of the tumor for proper diagnosis and management. CCOC should be included in the differential diagnosis list of jaw swelling that associated with slow-growing mass and paresthesia in the affected jaw.

An Overview of Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors are a group of endocrine tumors that constitute 7% of all pancreatic neoplasms. They can be benign or malignant. Their presentation can vary from slow growing, non infiltrative, indolent masses to rapidly progressing, highly aggressive, metastasizing tumors. In the past, there was paucity of scientific data available about the diagnosis and treatment strategy of these neoplasms but in recent years, ongoing research has inferred much data regarding classification, prognostic stratification and therapy of pancreatic neuroendocrine tumors. In this chapter we will discuss epidemiology, clinical presentation and classification, diagnosis and management of these tumors. We will also deliberate about the latest developments in treatment of pancreatic neuroendocrine tumors with focus on recent studies done on this topic.