Significant Mitotic Activity Research Articles

Malignant Bone-Forming Neoplasm With NIPBL::BEND2 Fusion.

Conventional high-grade osteosarcomas are characterized by aggressive radiologic features, cytologic pleomorphism, and complex genomics. However, rare examples of osteosarcomas remain challenging due to unusual histology, such as sclerosing or osteoblastoma-like features, which may require molecular confirmation of their complex genetic alterations. We have encountered such a case in a 17-year-old man, who presented with a third metatarsal sclerotic bone lesion, found incidentally in the work-up of a foot trauma. The initial imaging revealed a lesion with sclerotic/blastic features proximally and lucent/lytic portion distally, findings interpreted consistent with osteoblastoma. The lesion was managed intra-lesionally with curettings and cryoablation; however, the microscopic findings were non-specific, showing a bland osteoblastic proliferation embedded in a densely sclerotic matrix. Subsequently, the patient developed two rapid recurrences; the first recurrence was treated similarly despite its associated soft tissue extension radiographically, and the histologic findings remained non-specific. The 2nd recurrence showed a large mass, with bone destruction and soft tissue extension and an open biopsy revealed features of osteosarcoma with lace-like osteoid deposition, albeit with uniform cytomorphology. The subsequent below knee amputation showed features compatible with high-grade osteosarcoma, including solid growth of uniform epithelioid cells, with vesicular nuclei and scant cytoplasm, set in a lace-like meshwork of osteoid matrix. There was significant mitotic activity and tumor necrosis. Tumor cells were positive for SATB2. Further molecular work-up was performed showing an unexpected NIPBL::BEND2 fusion, which has been previously reported in two cases of phosphaturic mesenchymal tumor (PMT). FGF23 (ISH) was performed and was negative. By DNA methylation profiling, unsupervised clustering and UMAP dimensionality reduction revealed grouping with high-grade osteosarcomas and not with the PMT group. The patient received chemotherapy post-amputation and is alive without evidence of disease, with 10-month follow-up. We report an aggressive, overtly malignant acral bone-forming tumor, harboring a NIPBL::BEND2 fusion. Further studies are needed to evaluate the recurrent potential of this fusion in osteosarcomas and its relationship with PMT.

Sporadic Hybrid Nerve Sheath Tumour Arising from a Vestibulocochlear Nerve: A rare Case Report

Hybrid peripheral nerve sheath tumors (HPNST) were first included in the 4th edition of the World Health Organization (WHO) Classification of Central Nervous System in 2016. These tumors are a combination of schwannoma and neurofibroma, and are typically found in the limbs, trunk, and soft tissues. In this case report, we present a rare intracranial localization of neurofibroma/schwannoma with histological examination. Our patient was a 36-year-old man without any tumor genetic syndromes. The tumor measured 1.6 × 1.1 cm and was completely excised. The pathology report showed no significant nuclear atypia, mitotic activity, or necrosis. At the time of writing, the patient is alive and well with no recurrence. It is important to note that HPNSTs are usually benign tumors, but can occur in various locations, including the intracranial region. Further studies with a larger number of cases are needed to determine the exact pathogenetic basis of these tumors.

Sporadic Hybrid Nerve Sheath Tumour Arising from a Vestibulocochlear Nerve: A Rare Case Report

Hybrid Peripheral Nerve Sheath Tumors (HPNST) were first included in the 4th edition of the World Health Organization (WHO) Classification of Central Nervous System in 2016. These tumors are a combination of schwannoma and neurofibroma, and are typically found in the limbs, trunk, and soft tissues. In this case report, we present a rare intracranial localization of neurofibroma/schwannoma with histological examination. Our patient was a 36-year-old man without any tumor genetic syndromes. The tumor measured 1.6 × 1.1 cm and was completely excised. The pathology report showed no significant nuclear atypia, mitotic activity, or necrosis. At the time of writing, the patient is alive and well with no recurrence. It is important to note that HPNSTs are usually benign tumors, but can occur in various locations, including the intracranial region. Further studies with a larger number of cases are needed to determine the exact pathogenetic basis of these tumors.

A RARE PRESENTATION OF SMALL CELL LUNG CARCINOMA METASTASIZING TO PHEOCHROMOCYTOMA

Abstract Introduction/Objective Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another unrelated tumor. We report an interesting case of a tumor-to-tumor metastasis of small cell lung carcinoma to pheochromocytoma of the adrenal gland. Methods/Case Report A 75-year-old female former cigarette smoker with a past medical history of hypertension presented with a two-day history of dyspnea and epigastric pain. Physical examination demonstrated elevated blood pressure only. A computerized axial tomography scan of the chest and abdomen showed an incidental 3.1 cm right adrenal mass and right hilar lymphadenopathy. Detailed biochemical workup showed elevated serum epinephrine, norepinephrine, and 24-hour urine metanephrine. Adrenalectomy showed a 5.8 cm tumor mass with solid lobulated yellow to pink-tan and focally hemorrhagic cut surfaces. Microscopic examination showed a neoplasm composed of two distinct components. The predominant component consisted of nests ("zellballen") of large polygonal cells with variable nuclear pleomorphism, abundant amphophilic to basophilic cytoplasm, and a delicate intervening fibrovascular stroma, without significant mitotic activity. The minor component was characterized by sheets and nests of "small blue cells" with round to ovoid nuclei, stippled nuclear chromatin pattern, scanty cytoplasm, patchy necrosis, and high mitotic activity (>20 mitoses per 10 HPF). Foci of small cell carcinoma deposits were also present in the lymphatic channels of pheochromocytoma. Immunohistochemical stains demonstrated cytoplasmic staining of predominant component tumor cells for synaptophysin, chromogranin, and the absence of staining for TTF-1, CK CAM 5.2, and Ki-67. However, minor component tumor cells demonstrated cytoplasmic staining for synaptophysin, membranous staining for CK CAM 5.2, and nuclear staining for TTF-1 and Ki-67(60%). A final diagnosis of composite pheochromocytoma (predominant) and small cell neuroendocrine carcinoma (minor) was rendered. The possibility of a” collision” tumor comprising primary small cell carcinoma of pulmonary origin metastatic to an adrenal pheochromocytoma in light of the patient's cigarette smoking history and the presence of right hilar lymphadenopathy was favored. The subsequent biopsy of the right subcarinal adenopathy showed small cell carcinoma. Results (if a Case Study enter NA) NA Conclusion To the best of our knowledge, this is the only case of metastasis to a pheochromocytoma from a small cell neuroendocrine lung carcinoma.

Primary Chest Wall Ewing Sarcoma with Indolent Behavior in an Elderly Male

Abstract Introduction/Objective Ewing sarcoma (ES) is the second most common primary malignant bone tumor, primarily affecting children and young adults within the first two decades of life. Over 80% of cases are positive for CD99 and exhibit a characteristic t(11;22) translocation resulting in an EWSR1::FLI1 fusion. Extraosseous ES is extremely rare and most reported cases occur in patients less than 50 years old. We report an unusual case of extraosseous ES arising from the chest wall in an elderly male that showed slow interval progression on imaging studies. Methods/Case Report An 83-year-old male with a past medical history of COPD and tobacco use presented to the emergency department for a mechanical ground level fall and a worsening cough over the prior week. Of note, he was found to have a 6.1 cm pleural based mass seven years prior. The patient was ultimately discharged home with recommended oncologic follow-up for this long-standing chest wall mass due to an increase in size on imaging. A PET scan showed a hypermetabolic subpleural mass in the right lower chest wall measuring 7.6 cm with invasion through the adjacent ribs and intercostal spaces into the adjacent soft tissue. A core biopsy was performed, which demonstrated a small round blue cell tumor diffusely positive for CD99 and Bcl-2, lacking significant mitotic activity and necrosis. Given the unusual clinical features, a next generation sequencing (NGS) panel for sarcoma fusions was performed and identified an EWSR1::FLI1 fusion, supporting the diagnosis of ES/primitive neuroectodermal tumor (PNET). Results (if a Case Study enter NA) NA Conclusion ES is relatively common as a primary bone tumor in children and young adults, but is rare in the chest wall and pleura and is extremely rare in the elderly. The clinical course for ES is typically aggressive. Diagnosis of ES can be challenging as CD99 positivity is nonspecific. The characteristic t(11;22) EWSR1::FLI1 fusion can be identified through FISH or NGS. At 83 years old, this is, to our knowledge, the oldest patient reported in the literature with this diagnosis. The slow interval growth of this mass over a period of seven years is also unusual. These combined clinicopathologic features are exceedingly unique and expand upon the reported spectrum and behavior of the Ewing’s family of sarcomas. The use of broad NGS panels among pathologists may result in increased identification of ES in unusual clinical settings in the future, while also providing more confident pathologic classification in challenging situations.

FRI214 Adrenal Adenoma With Biochemical Findings Suggestive Of Cushing's Disease

Abstract Disclosure: A. Calimag: None. U. Tarabichi: None. M. Ahmad: None. M. Kazi: None. Introduction: We are presenting a case of a young female with prior history of multiple endocrinopathies presenting with a left adrenal adenoma with biochemical findings suggestive of Cushing's disease. Case Presentation: A 22-year-old female with a history of Type 1 Diabetes Mellitus was found to have a left adrenal adenoma 2.8 cm on CT. Absolute washout of 85 % and a relative washout of 63%, having 12 Hounsfield units (HU) on the non-contrast phase, findings suggestive of a benign adenoma. Further work up including 1 mg Dexamethasone suppression test (DST) showed unsuppressed plasma ACTH 17 pg/ml and total cortisol 9.4 mcg/dL. 8 mg DST showed ACTH 12 pg/ml, AM cortisol 8.8 mcg/dL, and Dexamethasone 991 ng/dl. Late night salivary cortisol 0.07 ug/dl, and 0.09 ug/dl, 24 hr urine cortisol 40.7. Other labs showed Aldosterone level was normal at 6.7, Renin level was also normal at 1.1. 24 hr urine catecholamines were Norepinephrine 35 mcg/24 hr, Epinephrine 3.9 mcg/24 hr, while urine Metanephrine level was <0.24, and normetanephrine level at 0.34. TSH 1.2mcU/ml. One day prior to surgery ACTH level was suppressed at 2.1 pg/ml drawn from a different lab. MRI of the Pituitary showed a slightly enlarged pituitary gland with uniform contrast enhancement and no definite lesion. The patient underwent a laparoscopic left adrenalectomy. Pathology showed an adrenal cortical neoplasm consistent with adrenal cortical adenoma, with no significant cytologic atypia, mitotic activity, or necrosis. Immunoperoxidase stain, the tumor is positive for inhibin and negative for PAX8. Post-op she developed adrenal insufficiency which was treated with hydrocortisone. The follow-up cortisol level was 11.3 mcg/dL when the patient was off hydrocortisone. Discussion: In this case, the biochemical exam showed elevated cortisol with ACTH not fully suppressed at both 1 mg and 8 mg DST which was done twice, and normal 24-hour urine cortisol. Determining whether this is adrenal vs pituitary mediated was one of the clinical dilemmas of this case. Initially, the patient’s ACTH was unsuppressed however the day before surgery ACTH was suppressed and the patient’s cortisol level normalized after the left adrenalectomy. Immunoassays for ACTH levels may occasionally be susceptible to analytical errors. (1-2) There are several case series and studies mentioning assay interference when using Immulite Assay versus Cobas ACTH assay. (1-2) Therefore, it is important to analyze clinical findings and biochemical testing and if lab tests are discordant, recheck using a different analytical platform in a different lab or an alternate ACTH assay to confirm ACTH levels. (1-2)

Solitary Fibrous Tumor of the Pancreas: Analysis of 9 Cases With Literature Review.

Solitary fibrous tumor (SFT) has been increasingly reported in various anatomic sites. However, it is still extremely rare in the pancreas. Herein, we present the first series of primary pancreatic SFTs. Nine cases of primary pancreatic SFTs were analyzed. The mean age was 60 years (36 to 76y) with no sex predilection. Six tumors were in the head, 3 were in the tail. On imaging studies, tumors were described as a hypervascular mass, 2 revealed cystic areas, and 3 were favored to be neuroendocrine tumors. On biopsy, 2 cases were diagnosed as atypical spindle cell tumor; one was misdiagnosed as suspicious for sarcoma, and another case as metastatic renal cell carcinoma. Two were diagnosed as low-grade sarcoma and low-grade stromal tumor on frozen sections. Grossly, tumors were well-demarcated with a median size of 4cm (0.9 to 15cm). Microscopically, they were composed of ovoid to spindle tumor cells with no significant mitotic activity and were arranged in alternating hypercellular and hypocellular areas. Staghorn-like vessels and entrapped pancreatic parenchyma were also detected within all tumors. Tumor cells revealed diffuse/strong nuclear STAT6 expression in 7 of 8, CD34 in 7 of 9, and bcl-2 in 4 of 4 tested cases. One tested tumor harbored NAB2 - STAT6 fusion. Eight patients with available follow-up data were free of disease at a mean follow-up of 76 months (3 to 189mo). SFT should be considered in the differential diagnoses of mesenchymal neoplasms of the pancreas. Immunohistochemical nuclear STAT6 expression is a characteristic feature of SFT. Primary pancreatic SFTs seem to have favorable biological behavior in our series.

Clinicopathological features of dysembryoplastic neuroepithelial tumor: a case series

BackgroundDysembryoplastic neuroepithelial tumors are rare benign supratentotrial epilepsy-associated glioneuronal tumors of children and young adults. Patients have a long history of seizures. Proper surgical resection achieves long term seizure control. We describe the clinicopathological features of dysembryoplastic neuroepithelial tumor cases reported in our practice and review the published literature.MethodsAll cases of Pakistani ethnicity were diagnosed between 2015 and 2021 were included. Slides were reviewed and clinicopathological features were recorded. Follow-up was obtained. Extensive literature review was conducted.ResultsFourteen cases were reported. There were 12 males and 2 females. Age range was 9–45 years (mean 19 years). Majority were located in the temporal and frontal lobes. Duration of seizures prior to resection ranged from 2 months to 9 years with mean and median duration of 3.2 and 3 years, respectively. Histologically, all cases demonstrated a multinodular pattern, specific glioneuronal component, and floating neurons. Simple and complex forms comprised seven cases each. No significant nuclear atypia, mitotic activity, or necrosis was seen. Ki-67 proliferative index was very low. Cortical dysplasia was noted in adjacent glial tissue in four cases. Follow-up ranged from 20 to 94 months. Seizures continued following resection in all but one case but were reduced in frequency and intensity. In one case, seizures stopped completely following surgery.ConclusionClinicopathological features were similar to those in published literature. However, a marked male predominance was noted in our series. Seizures continued following resection in all but one case but were reduced in frequency and intensity. This series will help raise awareness among clinicians and pathologists in our part of the world about this seizure-associated tumor of children and young adults.

Primary Cutaneous Epithelioid Mesenchymal Tumor With a Novel ATP2B4::GLI1 Gene Fusion.

GLI1 gene alterations (rearrangement or amplification) have been found in several bone and soft tissue tumors including pericytic tumors, gastric plexiform fibromyxoma, gastroblastoma, and a various group of epithelioid tumors with regional recurrence or distant metastasis. In this article, we describe a case of primary cutaneous epithelioid mesenchymal tumor harboring hitherto not reported ATP2B4::GLI1 gene fusion. A 42-year-old man presented with a growing firm lesion on the left postauricular scalp. Microscopically, the shave biopsy specimen revealed a dermal-based nodular proliferation of relatively monotonous epithelioid cells with round to ovoid nuclei and pale eosinophilic cytoplasm, accompanied by prominent stromal vasculature. Significant cytologic atypia, necrosis, and mitotic activity were absent. The tumor cells were partially positive for CD34 and S-100 protein, but were negative for other markers, including SOX-10, keratins, and myogenic markers. An ATP2B4::GLI1 gene fusion was identified by next-generation sequencing. Array CGH was also performed, but it did not show relevant chromosomal copy number changes. Awareness of this rare cutaneous tumor, and thus, reporting of additional cases is necessary for further delineating its full clinicopathologic spectrum.

PA21 A rare case of diffuse infantile fibromatosis

Abstract Fibromatoses are a heterogeneous collection of tumours of the skin and soft tissue with a large variability in presentation. We present a case of diffuse infantile fibromatosis in a 17-day-old infant boy. He was born at 40 + 7 weeks gestation with a vacuum-assisted delivery following an uncomplicated pregnancy. On physical examination, there were two well-circumscribed circular plaques that coalesced centrally on his left elbow. The plaque measured 2 × 1 cm and was firm, nontethered and nontender. Full skin examination was otherwise normal. Histopathological examination showed hyperkeratotic skin with an attenuated epidermis overlying a dermally based bland-appearing spindle cell proliferation. The lesion was infiltrative throughout the dermis and was arranged in short fascicles and interdigitated with subcutaneous fat, which was extensively trapped by spindle cells. There was no significant atypia and mitotic activity was identifiable but not brisk. Immunohistochemical stains showed strong and diffuse reactivity for smooth muscle actin. Infantile fibromatosis is the childhood counterpart of musculoaponeurotic fibromatosis. It is a benign mesenchymal tumour of infancy and early childhood with diffuse proliferations of oval-to-spindled fibroblasts that infiltrate regional structures. There is a male predominance and in most cases is noted within the first 8 years of life. Clinically, it presents as an asymptomatic, white-yellowish mass that is nontethered to the overlying skin. Although any site may be involved, the majority of cases affect the upper limbs, head and neck region. Histological findings include a wide morphological spectrum. In infants, small oval cells appearing between primitive mesenchymal cells and fibroblasts are in a myxoid background. The cells are loosely arranged and infiltrate skeletal muscle and other regional structures. Peripheral lymphocytic inflammation blends with more cellular proliferation composed of spindle-shaped fibroblasts arranged in bundles and fascicles. There is no well-documented immunohistochemical profile. An important differential diagnosis to exclude is congenital/infantile fibrosarcoma, which, characteristically, has high cellularity, uniform herringbone pattern, high mitotic rate, and zones of haemorrhage and necrosis. In terms of management, as there is a high likelihood of local recurrence in 65% of cases, evidence supports complete excision with documented margins. Where the lesion is diffusely infiltrative, a partial resection to maintain the best postoperative function is recommended.

PD-L1 expression, morphology, and molecular characteristic of a subset of aggressive uterine tumor resembling ovarian sex cord tumor and a literature review

BackgroundUterine tumors resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm of unknown etiology and has undetermined malignant potential. The emergence of recurrent UTROSCT case reports has led to its initial identification as a tumor of low malignancy potential. Owing to its low incidence, we currently lack any in-depth studies regarding the subset of UTROSCTs that may be aggressive in nature. Here, we sought to identify unique characteristics in aggressive UTROSCT.Methods19 cases of UTROSCT were collected. Their histologic and tumor immune microenvironment were evaluated by three gynecologic pathologists. The gene alteration was also detected by RNA sequencing. For later analyses regarding differences between benign and malignant tumors, we supplemented our 19 included cases with additional reports from the literature.ResultsInterestingly, we found PD-L1 expression in stromal tumor-infiltrating immune cells (stromal PD-L1) was markedly higher in aggressive UTROSCT. Patients with high stromal PD-L1 (≥ 22.5 cells/mm2) had worse prognosis. When our cases were added with previous cases identified in the literature, we discovered that aggressive UTROSCT was more likely to have significant mitotic activity and NCOA2 gene alterations than benign UTROSCT. Consistence with those results, patients with significant mitotic activity and gene alteration of NCOA2 had worse prognoses.ConclusionsCollectively, high expression of stromal PD-L1, significant mitotic activity, and gene alteration of NCOA2 may be useful markers to predict aggressive UTROSCT.

S-100 Negative Granular Cell Tumor of Oral Cavity with Aggressive Clinical Behavior

Abstract Introduction/Objective Granular cell tumors (GCTs) are neoplasms with neuroectodermal (Schwann cell) differentiation that is typically benign and cured by surgical excision. These tumors characteristically display strong expression of S-100 protein. Similar tumors without expression of S-100 protein are called “S-100 negative granular cell tumors.” The few reported cases of S-100 negative GCT in the oral cavity describe indolent clinical behavior. We report a case of a 49-year-old male with recurrent S-100 negative GCT in the oral cavity. Methods/Case Report The patient presented initially with a mass in the hard palate, which was resected and diagnosed as an S-100 negative GCT. One year later, the patient developed severe epistaxis and anemia (hemoglobin 7.2 g/dL). A large tumor of the hard palate was the source of bleeding. It was resected and diagnosed as recurrent S-100 negative GCT. Histologically, this tumor consists of small nests of epithelioid to spindled cells with moderately abundant granular eosinophilic cytoplasm, round central nuclei with vesicular chromatin and distinct eosinophilic nucleoli, and significant mitotic activity. The cells are immunoreactive for SOX10 and negative for S-100, melan-A, keratin AE1/AE3, p40, synaptophysin, smooth muscle actin, desmin, and myogenin. Results (if a Case Study enter NA) N/A Conclusion S-100 negative GCTs are rare, and only a few case reports describe their involvement in the oral cavity. We report this case because of its rarity and aggressive clinical behavior. Recognition of this entity and its potential for locally aggressive growth is important. Management of this tumor by complete excision seems advisable.

Lipoblastoma-like tumor of the vulva: A rare benign mesenchymal neoplasm mimicking myxoid liposarcoma

Abstract Introduction/Objective Lipoblastoma-like tumor of the vulva (LLTV) is a rare, benign mesenchymal neoplasm of adipocytic differentiation that typically presents as a vulvar mass in young women, clinically mimicking a Bartholin gland abnormality. The tumor is well-circumscribed and multilobulated, composed of mature adipocytes, uniloculated lipoblasts and bland spindle cells. Morphologic features often overlap with lipoblastoma, myxoid liposarcoma, and spindle cell lipoma; however, absent alterations of PLAG1 and HMGA2 distinguish it from lipoblastoma, and lack of DDIT3 gene rearrangement distinguishes it from myxoid liposarcoma. While Rb1 usually demonstrates a “mosaic” pattern of expression, no definitive evidence of a structural abnormality in 13q has been identified. Methods/Case Report A 24-year-old female presented with mild discomfort and persistent swelling of the right vulva for one year, which was initially thought to be a Bartholin gland cyst. Physical examination revealed marked asymmetry between the right and left vulva, and ultrasound examination revealed an ovoid, hypoechoic, and solid- appearing vulvar mass (4.7 x 2.5 x 1.1 cm). She subsequently underwent excision of the vulvar mass for diagnosis and treatment. Results (if a Case Study enter NA) The excision specimen showed a relatively well-circumscribed and multi-lobulated subcutaneous mass with myxoid stroma and thin fibrous septa. The tumor was composed of a mixture of bland spindle cells, uniloculated lipoblasts and mature adipocytes. No significant nuclear atypia, necrosis or mitotic activity was identified. Immunohistochemical stains showed that the tumor cells were negative for keratin cocktail, S100 protein, SMA, and Desmin. CD34 highlighted vessels within the lesion, and Rb1 showed a "mosaic" pattern of weak and negative expression. Conclusion Lipoblastoma-like tumor of the vulva (LLTV) is a rare, benign tumor that tends to occur in young women, often clinically mimicking a Bartholin gland cyst. Recognition of this rare entity with distinction from mimics including myxoid liposarcoma is essential to avoid overly aggressive treatment. Complete conservative excision is recommended.

TRAF7-mutated Fibromyxoid Spindle Cell Tumors Are Associated With an Aggressive Clinical Course and Harbor an Undifferentiated Sarcoma Methylation Signature: A Molecular and Clinicopathologic Study of 3 Cases.

TRAF7 somatic mutations are rare and have been reported in meningiomas, intraneural perineuriomas, and mesotheliomas. Triggered by an index case of an unclassified low-grade mesenchymal tumor with TRAF7 mutation as the only genetic alteration, we searched our files and identified 2 additional cases with similar features. The tumors arose in 2 females and 1 male, aged 63 to 75 years old (median: 67y). They were infiltrative deep soft tissue masses involving the shoulder, chest wall, and thigh, measuring 7.0 to 9.1cm in greatest dimensions. One tumor was locally aggressive, and 2 were associated with lung and bone metastases. The tumors displayed alternating fibrous and myxoid stroma with mild to moderate cellularity and consisted of uniform spindle cells with open chromatin, inconspicuous nucleoli and scant cytoplasm. Significant mitotic activity or necrosis were not present. However, the metastatic tumor of 1 case showed an epithelioid morphology and brisk mitotic activity. Immunohistochemically, the tumors showed nonspecific and focal smooth muscle actin or CD34 expression. By DNA sequencing, all 3 cases harbored TRAF7 missense mutations involving the C-terminal WD40 domains as the only somatic mutations, showed nonrecurrent focal copy number alterations, and were negative for gene fusions by targeted RNA sequencing. On methylation profiling, the tumors clustered with the undifferentiated sarcoma and myxofibrosarcoma methylation classes and were distinct from morphologic mimics. On follow-up (5 to 36mo), 2 patients died of disease following aggressive chemotherapeutic regimens. We describe a novel TRAF7- mutated mesenchymal tumor characterized by aggressive clinical behavior despite the histologic appearance of a low-grade fibromyxoid spindle cell tumor.

S2076 Not an Ordinary Intussusception: A Sigmoid Diverticula With an Extra-Colonic Mass

Introduction: Intussusception is defined as telescoping of a segment of the gastrointestinal tract into an adjacent lumen frequently found in childhood and are rarely found in adults. Etiologies of intussusception include benign or malignant tumors and idiopathic causes. Diverticula are rare findings for intussusception. This is a case of a patient found to have an intussusception due to a sigmoid diverticula and found to have a pelvic mass isolated outside of the diverticula. Case Description/Methods: An 80-year-old White female presented for worsening abdominal pain, nausea, and vomiting. History otherwise was unremarkable. CT of the abdomen and pelvis demonstrated a small bowel obstruction with a transition point in the left lower abdomen and a large 12.7x10.4 cm necrotic right pelvic mass involving the sigmoid colon (Figure 1A). The patient underwent a flexible sigmoidoscopy and endoscopic ultrasound. Endoscopic findings demonstrated an intusscepting large diverticulum at 40 cm and a peri-sigmoid heterogenous vascular mass on endosonography (Figure 1B and 1C). The patient underwent surgical resection of the mass, which upon resection demonstrated a mass arising from the sigmoid diverticulum isolated off the true colonic wall. Pathology demonstrated a 10.5 cm smooth muscle tumor concerning for a leiomyoma of deep soft tissue which did not involve the muscularis mucosae; staining was positive for muscle markers, no significant mitotic activity on Ki-67 mitotic proliferation markers, CD117, DOG1 were negative. Post operatively the patient did well. Discussion: Adult Intussusception are commonly due to colonic masses and are rarely associated with diverticula. This case highlights a patient who was found to have a sigmoid diverticulum as the etiology for intussusception and found to have an associated colonic mass as an extension from the diverticula isolated from the colonic wall. This diverticulum was likely a result of the chronic mass creating tethering of the bowel to the area. Masses arising from diverticula are rare and the majority of mases are found upon evaluation of other symptoms (pain and bleeding). In this patient, pathology demonstrated a leiomyoma which are rare benign tumors that are generally asymptomatic and found incidentally. During endoscopy, outside of a diverticula there was no obvious mass until endoscopic ultrasound was done. Therefore, this case highlights how critical it is for endoscopists to have a low threshold for further work up despite an unrevealing endoscopy.Figure 1.: A (Top Left), CT Scan of abdomen and pelvis with large necrotic mass. B (Top Right), Endoscopic view of diverticula. C (Bottom Left), Endoscopic ultrasound of necrotic mass.

Automated in vivo compound screening with zebrafish and the discovery and validation of PD 81,723 as a novel angiogenesis inhibitor

Angiogenesis is a critical process in tumor progression. Inhibition of angiogenesis by blocking VEGF signaling can impair existing tumor vessels and halt tumor progression. However, the benefits are transient, and most patients who initially respond to these therapies develop resistance. Accordingly, there is a need for new anti-angiogenesis therapeutics to delay the processes of resistance or eliminate the resistive effects entirely. This manuscript presents the results of a screen of the National Institutes of Health Clinical Collections Libraries I & II (NIHCCLI&II) for novel angiogenesis inhibitors. The 727 compounds of the NIHCCLI&II library were screened with a high-throughput drug discovery platform (HTP) developed previously with angiogenesis-specific protocols utilizing zebrafish. The screen resulted in 14 hit compounds that were subsequently narrowed down to one, with PD 81,723 chosen as the lead compound. PD 81,723 was validated as an inhibitor of angiogenesis in vivo in zebrafish and in vitro in human umbilical vein endothelial cells (HUVECs). Zebrafish exposed to PD 81,723 exhibited several signs of a diminished endothelial network due to the inhibition of angiogenesis. Immunochemical analysis did not reveal any significant apoptotic or mitotic activity in the zebrafish. Assays with cultured HUVECs elucidated the ability of PD 81,723 to inhibit capillary tube formation, migration, and proliferation of endothelial cells. In addition, PD 81,723 did not induce apoptosis while significantly down regulating p21, AKT, VEGFR-2, p-VEGFR-2, eNOS, and p-eNOS, with no notable change in endogenous VEGF-A in cultured HUVECs.

Pituitary adenoma-Gonadotroph type in a 47 years old female patient: A case report

Pituitary adenomas are tumors of the anterior pituitary. Most pituitary tumors are slow-growing and benign. They are classified based on size or cell of origin. Pituitary adenoma can be classified as microadenoma, macroadenoma, and giant tumors based on size.Pituitary adenomas are mostly found incidentally on imaging modalities obtained for other reasons. Mutations in known Oncogenes have little role in the pathogenesis of most sporadic pituitary adenomas. Case presentation : A 47 years old female patient presented with complain of diminished vision , severe headache and dizziness since 1 months.MRI was advised which showed an ill-defined low signal intensity lesion of approximate 3.4x3.2x3 cm noted in clivus, bilateral spenoid sinus and sella region. Histologically, near-signature appearance is that of elongated cells surrounding blood vessels in a pseudorosette-like ependymoma-mimicking pattern. cells with small round nuclei and there is no significant mitotic activity. Conclusion : Pitutary adenoma-gonadotroph type is benign and can cause symptoms from mass effect or by effecting the level of the hormones. Differetial diagnosis includes ependymoma, Pitutary blastoma, Pitutary nodular hyperplasia, dermoid cyst, low grade astrocytoma, meningioma, rathke cleft cyst.

Cystitis Cystica and Cystitis Glandularis of the Urinary Bladder: A Review and Update

Cystitis Cystica and Cystitis Glandularis of the Urinary Bladder: A Review and Update

SUPERFICIAL MYOFIBROBLASTOMA OF THE GENITAL TRACT : A CASE REPORT OF VAGINAL SMFGT

Superficial myofibroblastoma of the lower female genital tract is a rare benign, recently recognized neoplasm that mostly affects the vulvovaginal area. In this paper we reported a case of 47years old lady who had 3-Normal vaginal deliveries , she had presented with complain of dysuria , difficult micturition lower abdominal pain, heaviness in the vagina and vaginal discharges. Vaginal examination showed a well demarcated , smooth mass measuring about 7cm x3cm. Transvaginal ultrasound was performed which showed a well -defined isoechoic solid lesion with heterogenous echo pattern which occupied the upper portion of the anterior vaginal wall. Magnetic resonance imaging showed a lesion described as a well defined mass at the level of anterior vaginal wall measuring 3.1APX4.5TVX3.3CC cm. The mass was removed per vaginal route , histopathologically, the tumor was characterized by nodular stromal spindle cell lesion, well defined and partly encapsulated with myxoid degeneration and prominent vascular network. No necrosis is seen .No significant mitotic activity indentified. The findings were consistent with superficail myofibroblastoma. Immunohistochemistry stain was carried out which was positive for CD34, Desmin , Vimentin and weakly positive for ER.

28323 Cutaneous leiomyosarcoma in scope of practice for dermatologists

Leiomyosarcomas (LMS) are malignant neoplasms primarily deriving from smooth muscle. Historically, LMS are classified as cutaneous or subcutaneous. We describe a 68-year-old male with a 2.5 × 2.3 cm firm nodule growing for 6 months on the right thigh. Pathology shows sheet-like proliferation of markedly atypical ovoid to spindled cells arranged in intersecting fascicles with significant mitotic activity, and pleomorphism diagnostic of cutaneous LMS. Immunohistochemistry confirmed that tumor cells are positive for smooth muscle actin and focal desmin, but negative for CD34, pancytokeratin, EMA, Melan-A, p63, and S-100. CT scans revealed no metastasis to the chest nor quadriceps invasion. Although the initial excision for diagnosis revealed negative inked margins, complete excision with 2 cm margin was performed because of focal subcutaneous extension. Cutaneous LMS demonstrates a predilection for the lower limbs (50-75% of cases) of Caucasian males after the fifth decade of life. Evaluation of the entire depth of LMS is essential since cutaneous and subcutaneous LMS exhibit different clinical behaviors. Cutaneous LMS has even been reported recently with a similar prognosis as atypical fibroxanthoma. Complete surgical excision or Moh's is curative for cutaneous LMS, while no targeted therapy exists for subcutaneous LMS and it responds poorly to conventional chemotherapy or radiation therapy. Because cutaneous LMS is rare, no consensus exists on appropriate surgical margins. Cutaneous LSM rarely metastasize. However, subcutaneous extension of cutaneous LMS may increase risk of recurrence. Although 1 cm margin may be adequate for cutaneous LMS, wider margins may be required if any subcutaneous infiltration exists.