Cm In Maximum Dimension Research Articles

Clinicopathological Characteristics of Neutrophil-Rich Hepatocellular Carcinoma: An Uncommon Subtype of Primary Liver Cancer.

Introduction. Neutrophil-rich hepatocellular carcinoma (HCC) is an extremely uncommon subtype of HCC with an overall incidence of <1%. Neutrophil-rich HCC shows poor cellular differentiation and sarcomatoid transformation in most patients. There is prominent neutrophilic inflammatory cell infiltration in the tumor. These tumors are associated with poor prognosis, high rate of recurrence, and metastasis. Methods. Herein, we investigated 4 patients with neutrophil-rich HCC reported at our center. Clinical, radiological, and pathological findings were reviewed. Immunophenotypic characterization of the tumors were done. Granulocyte colony-stimulating factor (G-CSF), programmed cell death ligand 1 (PD-L1), and mismatch repair immunostains were performed in all 4 tumors. Results. We report 4 neutrophil-rich HCCs in 3 male patients and one female patient with an age range of 43 to 64 years. Three underwent living donor liver transplantation and one underwent right hepatectomy. Tumor measured 0.5 cm to 12 cm in maximum dimension. Histologically, tumors demonstrated moderate to marked cellular pleomorphism. Spindle cell transformation was noted in 3 tumors. Three tumors showed vascular invasion, and one tumor showed bile duct invasion. Immunopositivity for Hep Par-1, arginase-1, and glypican-3 was present in all tumors. Tumors also expressed stemness markers including KRT19 and EpCAM. Cytoplasmic positivity for G-CSF and immunoexpression of PD-L1 was demonstrated. We also report proficient mismatch repair by immunohistochemistry in all tumors. Conclusion. Neutrophil-rich HCC is an aggressive primary liver cancer which demonstrates stemness-related features. Programmed cell death ligand 1 expression in tumor cells suggests distinct immunogenic features and potential role of anti-PD-L1 therapies in inoperable disease.

A Case Report of Inflammatory Myofibroblastic Tumor Mimicking Leiomyosarcoma of the Uterus

Abstract Introduction/Objective Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare entity that presents significant diagnostic challenges due to its infrequency and has the potential for being misdiagnosed as a leiomyoma, endometrial stromal tumor, or myxoid leiomyosarcoma, resulting in undertreatment or overtreatment. Methods/Case Report We present a case report of a 50-year-old woman with a history of anemia due to heavy menstruation caused by fibroids, who underwent hysterectomy. The concurrent pelvic wash cytology raised suspicious for myxoid leiomyosarcoma. Results (if a Case Study enter NA) Macroscopic examination revealed both well and poorly circumscribed nodules, ranging upto 4.7 cm in maximum dimension. Cut surfaces exhibited a spectrum of appearances, including tan-pink, whorled and rubbery, as well as soft, hemorrhagic, edematous, and mucinous areas with necrosis. Microscopically, the tumor exhibited myxoid spindle cell proliferation, in the background of lymphoplasmacytic inflammatory infiltrates. She was diagnosed with IMT metastasis to left fallopian tube, ovary, and omentum. Immunohistochemical (IHC) analysis further confirmed the diagnosis, showing strong and diffuse cytoplasmic positivity for ALK (anaplastic lymphoma kinase), caldesmon, and smooth muscle actin. This case underscores the critical importance of accurate diagnosis in guiding appropriate treatment strategies. Moreover, given the morphological overlap with other uterine tumors, the identification of ALK rearrangement emerges as a pivotal diagnostic marker, distinguishing IMT from its mimics such as leiomyoma, leiomyosarcoma and smooth muscle tumor of uncertain malignant potential (STUMP). Enhancing our understanding of the histomorphological features and ALK immunostaining of uterine IMT is essential for optimizing patient management and outcomes. Conclusion IMT in the female genital tract can mimic other more common benign and malignant tumors like leiomyoma, leiomyosarcoma, and endometrial stromal sarcoma. Familiarity with clinical and histologic features and the use of ALK immunostaining can be critical for correct diagnosis.

12345 Staying Ahead of Cowden’s Syndrome in Differentiated Thyroid Cancer

Abstract Disclosure: M.S. Gordon: None. M.B. Gordon: None. Cowden’s syndrome or multiple hamartoma syndrome, is an uncommon autosomal dominant genodermatosis and is a member of the spectrum of disorders involving mutations in the phosphatase and tensin homolog gene (PTEN). It is associated with differentiated thyroid cancer (DTC), ¾ papillary, including follicular variant (FVPTC), 1/4 follicular (FTC), and other malignancies, including breast (most common), colorectal, renal cell, endometrial and skin cancers. We report a case of Cowden’s syndrome in which the patient presented with FVPTC but had no other apparent indication of a genetic abnormality until she was found to have a melanoma and was noted to have macrocephaly. The patient presented at age 26 with a thyroid nodule of 2.7 cm in maximal dimension. FNA was benign. By age 31 the lesion had grown to 3.3 cm and a repeat FNA showed a follicular neoplasm. She underwent left lobectomy and isthmusectomy revealing a 3.0 cm FVPTC with focal Hurthle cell features. There was capsular irregularity, and subsequently she underwent completion thyroidectomy showing a right sided 8mm FVPTC. She then received 30 mCi I 131. There were no apparent pathologic mucocutaneous lesions, intellectual deficits, and no family history of Cowden’s syndrome. At age 39 she was found to have a Stage IA malignant melanoma of the periumbilical skin which was resected. With two malignancies diagnosed at a relatively young age, she was evaluated for genetic syndromes and it was simultaneously noted that she had macrocephaly with head circumference of 66 cm. (&amp;gt;99 percentile). An analysis of 69 genes by Ambry genetics revealed a pathogenic variant in the PTEN gene (c.388 C&amp;gt;T (p.R130*). PTEN R130* results in a premature truncation of the PTEN protein at amino acid 130 of 403 within the phosphatase tensin-type domain resulting in loss of function. Macrocephaly (2% population frequency) is seen in 80% of patients with PTEN mutations. Twenty percent of patients with thyroid carcinoma and macrocephaly have a PTEN mutation and lifetime risk of melanoma in DTC is 25%. BRAF and RAS mutations may cooperate with PTEN loss and explain the increased co-occurrence of malignancies with BRAF and RAS mutations such as melanoma, FTC, and PTC in Cowden’s syndrome. In conclusion, we suggest that head circumference should be measured in all patients with DTC to screen for PTEN abnormalities. Patients with DTC also should have a thorough skin examination. Presentation: 6/2/2024

Pedunculated Angiomyofibroblastoma of Labia Minora: A Case Report and Review of the Literature

Background: Angiomyofibroblastoma was first described by Fletcher et al. in the year 1992. It is a distinctive benign tumor that most often occurs in the superficial area of the vulva and is rarely reported in men in the inguinoscrotal region. Case Presentation: A 23-year-old female presented with a painless pedunculated labial mass which was initially pea-sized and reached 7 cm in maximum dimension over four months. The case was diagnosed on morphology, IHC and the patient was treated surgically. The interesting feature of the case was the rarity of its incidence at labia minora and pedunculated form and its resemblance to other benign and more aggressive tumours. To the best of our knowledge, the extensive English literature search revealed only seven cases of pedunculated angiomyofibroblastoma at labia majora in middleaged female and one case of labia minora in a young female. Conclusion: The lesion must be differentiated from another benign mesenchymal tumor of vulva which requires extensive surgical management.

Pulmonary gangliocytic paraganglioma: An under-recognized mimic of carcinoid tumor

Gangliocytic paragangliomas are rare neoplasms occurring almost exclusively in the ampullary region of the gastrointestinal tract. Although these tumors are not typically considered in the differential diagnosis of primary pulmonary neoplasia, 5 cases of primary pulmonary gangliocytic paragangliomas have been previously reported. Herein we report our experience with 3 additional examples, all referred to our Anatomic Pathology Consultation service. The patients (a 32-year-old man, a 69-year-old woman and a 55-year-old man) each presented with an endobronchial (2 cases) or upper lobe lung mass, ranging from 1.5 to 2.5 cm in maximum dimension. Biopsy and endobronchial debulking specimens demonstrated the classic triphasic morphology of gangliocytic paraganglioma, with epithelial, spindled and ganglion-like cells. By immunohistochemistry, the tumors were positive for keratin, synaptophysin and chromogranin A in the epithelial component, S100 protein and glial fibrillary acidic protein (GFAP) in the Schwannian spindled cells, and synaptophysin in ganglion cells. TTF1 expression was seen in the epithelial components of 2 cases. The Ki-67 labelling index was low (<2%). Primary pulmonary gangliocytic paragangliomas should be distinguished from carcinoid tumors, given the different natural histories and risk stratification approaches for these morphologically similar tumors. Awareness that gangliocytic paraganglioma may occur in the lung and appropriate immunohistochemical studies are key to correct diagnosis.

HPB P54 First Reported Case of Primary Serous Cystadenocarcinoma of the Spleen

Abstract Background Tumours of the spleen are uncommon, and the majority are metastases from primary malignancies in other organs. The two main subdivisions of primary malignancies of the spleen are lymphoid and non-lymphoid. Primary splenic cystadenocarcinomas are extremely rare, and only tumours of the mucinous subtype have been recorded. The spleen usually exhibits secondary infiltration from primary cystadenocarcinomas in other organs such as the ovaries and pancreas. Methods We present the case of an elderly white female who was found to have an incidental splenic tumour. This showed interval increase in size on serial imaging and was confirmed to be a complex mass with a cystic component on MRI. After MDT discussion and further investigations, including FDG-PET, EUS and diagnostic laparoscopy, she underwent a distal pancreatectomy, partial gastrectomy and splenectomy for a presumed tail of pancreas adenocarcinoma. Results The splenic hilum contained a large partly cystic tumour conglomerate measuring up to 5.8cm in maximum dimension, which contained thick, dark red, gelatinous material. It was well-circumscribed and demarcated from the rest of the splenic parenchyma, and the distal pancreas appeared to be uninvolved. Histology showed low columnar to cuboidal cells with moderate to patchy marked nuclear pleomorphism, and no cytoplasmic mucin was identified. The tumour had a predominantly papillary and focal tubular architecture, with hierarchical branching of papillae. The neoplastic cells stained positive for CK7, ER and WT1 expression and negative for CK20 and CA. Conclusions Histological and immunohistochemical analyses were consistent with the first recorded case in the literature of primary serous cystadenocarcinoma of the spleen, which we believe developed through malignant transformation of a benign epidermoid cyst. This is the commonest type of true cysts of the spleen and one which has tumorigenic potential, being able to undergo metaplasia and dysplasia. The patient remains well as per her latest follow-up with no evidence of recurrence or metastases. However, given the rarity of splenic cystadenocarcinomas, uncertainty remains on the long-term prognosis and optimal management of such cancers, including adjuvant treatment options.

Development and validation of a predictive model assessing the risk of seizure recurrence in children with neurocysticercosis

IntroductionNeurocysticercosis (NCC) is a significant factor contributing to the incidence of seizures in developing countries. While numerous studies have investigated the recurrence of seizures in NCC, their reliability is often limited. MethodsWe assessed the socio-demographic, clinical, and neuroimaging details of 161 children with seizures caused by NCC. We monitored them for seizure recurrence over a 6-month follow-up period. We divided the children into two groups: those with seizure recurrence and those without. Subsequently, we identified predictive factors associated with seizure recurrence through univariate analysis, followed by multivariate binary logistic regression. We evaluated the prognostic model for discrimination and calibration and then internally validated it using the bootstrap method. ResultsA total of 23 children experienced breakthrough seizures. In multivariate analysis, the presence of epileptiform abnormalities in electroencephalogram (EEG), more than 5 NCC lesions, the presence of perilesional edema greater than 2 cm in maximum dimension, and a cluster of seizures before presentation were significantly associated with seizure recurrence (p < 0.05). These factors were included in the final NEPC (Number of NCC lesions, Epileptiform EEG abnormality, Perilesional edema, and Cluster of seizures) score. The final model exhibited good discrimination (AUC = 89.1 %; 95 % CI=80.5–95.3 %, p < 0.001) and calibration (p = 0.54). A score of 4 appeared to be the optimal threshold for discriminating between individuals with and without seizure recurrence, with sensitivity and specificity values of 85 % and 87 %, respectively. Interrater reliability was very strong between two pediatric neurologists and strong between a pediatric neurologist and a pediatric neurology trainee resident (k = 0.92 and 0.86, respectively). ConclusionThe NEPC score demonstrates good sensitivity and specificity in predicting seizure recurrence in pediatric children with NCC.

THU618 Adrenal Cell Carcinoma Presenting With Post-menopausal Bleeding And IGF-2 Induced Hypoglycaemia

Abstract Disclosure: E.M. Lonergan: None. L.J. Tan: None. E. Ali: None. C.M. Joyce: None. N. Conlon: None. A. O'Sullivan: None. D.J. O'Halloran: None. Background: Non-islet cell tumour hypoglycaemia (NICTH) as a result of IGF-2 secretion is rare with a few case reports associated with adrenal tumours. Clinical Case: We present the case of a 59-year-old female initially presenting to gynaecology services with post-menopausal bleeding due to endometrial hyperplasia. Serum testosterone, oestradiol and adrenal androgens were found to be elevated and LH and FSH suppressed. A subsequent CT adrenals demonstrated a 12.8 x 13.2 x 10.6cm left adrenal mass and she failed a 1mg overnight dexamethasone suppression test. In the interim, while undergoing evaluation, the patient presented to A+E Department with point-of-care confirmed hypoglycaemia with a capillary blood glucose of 1.6mmol/L and neuroglycopaenic symptoms. There was no history of diabetes mellitus, prolonged fasting, access to sulphonylureas or insulin. During a supervised fast, symptomatic hypoglycaemia occurred within 5 hours at 2.0mmol/L fulfilling Whipple’s triad. Results of samples taken during hypoglycaemia revealed an elevated IGF-2 : IGF-1 ratio of 60.7 (normal &amp;lt;10) with a low paired C-peptide, insulin and pro-insulin, consistent with a suspected IGF-2-secreting tumour. Hypoglycaemia was successfully managed with low glycaemic index foods and clinical nutrition input. Radical surgical excision was undertaken including left adrenalectomy, nephrectomy, partial pancreatectomy and splenectomy. Post-operative pathology revealed an adrenocortical carcinoma (ACC) measuring 16.4cm in maximum dimension; Ki67 12%; Weiss score 5; lymph nodes negative. Tissue has been stained for IGF-2-IR. Post-operative IGF-2 : IGF-1 ratio normalised to 3.4. The patient is under active follow up with 3-monthly surveillance CT-TAP and has declined Mitotane therapy at present. Conclusion: This is a rare case of ACC secreting multiple hormones, resulting in post-menopausal bleeding and IGF-2 mediated hypoglycaemia. Presentation: Thursday, June 15, 2023

FRI265 I123-MIBG Positive, CU64-Dotatate PET Negative Pheochromocytoma In A Patient With Bilateral Adrenal Incidentalomas

Abstract Disclosure: P. Pagadala: None. V. Patel: None. Bilateral incidental adrenal nodules represent 10-23% of all incidental adrenal nodules. Most are benign nonfunctioning adenomas however these can be catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla called pheochromocytomas. Identifying pheochromocytoma using anatomic imaging alone in cases of bilateral adrenal nodules is challenging. Functional imaging with radioisotope tracers can be helpful such as MIBG (meta-iodobenzylguanidine) and DOTATATE scans. We describe a case of pheochromocytoma, which was negative on DOTATATE but positive on MIBG scan which localized the pheochromocytoma. A 65-year-old male with a history of hypertension, chronic kidney disease and obstructive sleep apnea was found to have bilateral adrenal nodules on routine imaging. MRI abdomen showed a right adrenal nodule 1.7cm x 1.8cm x 1.7cm and a left adrenal nodule 2.3 cm in maximum dimension. He had no apparent symptoms of catecholamine excess. Biochemical testing revealed elevated total plasma metanephrines on serial assessments along with elevated 24-hour urine dopamine levels. A CT scan with adrenal protocol further characterized the right adrenal nodule with precontrast density of 43 Hounsfield Units (HU) with a rapid washout of 75% within 5 minutes, consistent with benign adrenal adenoma. The left adrenal gland had 2 nodules. A smaller superior nodule 1.3 cm AP x 1.0 cm transverse x 0.9 cm craniocaudal in size, density of -3 HU on the precontrast images, with approximately 85% washout most consistent with a benign adrenal adenoma. A larger inferior nodule was 2.3 cm AP x 2.2 cm transverse x 2.3 cm craniocaudal in size and precontrast density of 32 HU, rising to 58 HU during the portal venous phase and remaining at about 58 HU on the delayed images, indicating no significant washout and is indeterminate. A Cu64 labeled DOTATATE scan showed the 1.6 cm right adrenal nodule demonstrated activity similar to that of contralateral background adrenal activity. There was no comment regarding the two left adrenal nodules. A I123 MIBG scan showed the larger of the two left adrenal nodules had a strong uptake of the MIBG highly likely to be a pheochromocytoma. The smaller left adrenal nodule and the right adrenal nodule had no significant MIBG uptake, making these adrenal adenomas. The patient underwent left robotic adrenalectomy and pathology confirmed a 2.3 cm pheochromocytoma in addition to adrenocortical nodular disease. Three months post-surgery, plasma and 24-hour urinary measurements for metanephrines and catecholamines had normalized. Further research is needed to assess the benefit of I123MIBG when DOTATATE is negative. A potential cause of false negatives on DOTATATE is variability in somatostatin receptor subtype expression. Better imaging modalities for pheochromocytomas and guidelines for the management of bilateral adrenal nodules would assist in treatment decisions. Presentation: Friday, June 16, 2023

A Comparison of Local Failure and Necrosis Following Different Radiosurgery Strategies for Large Brain Metastases

Large brain metastases (LBMs) are associated with poor local control with single-fraction stereotactic radiosurgery (SRS) alone. Various alternative strategies have been developed, including fractionated SRS (FSRS) and staged SRS (SSRS) for intact LBMs, and resection with postoperative-SRS (postop-SRS) or preoperative-SRS (preop-SRS) for operable LBMs. The objective of this study is to compare local failure (LF) and radiation necrosis (RN) outcomes among these four management strategies to determine the optimal treatment paradigm. Consecutive patients diagnosed with LBM (≥2 cm in maximum dimension) between July 2017 and January 2022 and treated with one of the aforementioned strategies at a single tertiary institution were evaluated. All immobilization, target contouring, margins, dose- and prescription selection followed pre-defined institutional guidelines. Primary endpoints included LF, symptomatic RN, or a composite endpoint of these two variables. Gray's test was used to compare the cumulative incidence of the LF and the composite endpoint, with death as a competing risk. A total of 234 LBMs in 188 consecutive patients met the inclusion criteria. The median age was 65 years (range: 31-98), the median KPS was 80 (range: 50-100), and 58% were female. The most common primary tumors were lung (48%) and breast cancer (17%). The median maximum tumor diameter was 3.0 cm (range: 2.0-5.6). 47 (20%) lesions were treated with FSRS, 66 (28%) with SSRS, 74 (32%) with postop-SRS, and 47 (20%) with preop-SRS. With a median follow-up of 12 months, 22 (9%) LF and 11 (5%) RN events occurred. The 6-month and 1-year cumulative incidences of LF for the entire cohort were 5% (95% CI: 3%-9%) and 8% (95% CI: 5%-12%), respectively. The 6-month and 1-year LF rates were 4% (95% CI: 1%-13%) and 8% (95% CI: 3%-20%) for FSRS; 8% (95% CI: 3%-20%) and 8% (95% CI: 3%-20%) for SSRS; 7% (95% CI: 3%-15%) and 8% (95% CI: 3%-16%) for postop-SRS; 0 and 7% (95% CI: 2%-20%) for preop-SRS (p>0.05). The 1-year OS rates were favorable in resected patients (61% for postop-SRS and 82% for preop-SRS) compared to SRS alone strategies (45% for FSRS and 56% for SSRS) (p = 0.004). Similarly, RN events were significantly lower in resected patients treated with either bimodality approach (0 for postop-SRS and 4% for preop-SRS) than SRS standalone strategies (9% for FSRS and 8% SSRS) (p = 0.024). At 12 months, the cumulative probabilities of the composite endpoint were 13% (95% CI: 5%-25%) for FSRS, 15% (95% CI: 7%-25%) for SSRS, 9% (95% CI: 3%-17%) for postop-SRS, and 12% (95% CI: 4%-24%) for preop-SRS and not significantly different between the groups. For medically operable patients with surgically resectable LBMs, a strategy of surgery and SRS, regardless of timing, is associated with favorable local control and reduced risk for RN. For unresected patients, either SSRS or FSRS is associated with similar local control, but slightly higher RN risk. Prospective comparative evaluation is warranted.

Safety, feasibility, and quality of thulium laser en-bloc resection for treatment of non-muscle invasive bladder cancer

BackgroundTrans-Urethral Resection of Bladder Tumors (TURBT) is a critical step in diagnosis, staging and treatment of bladder tumors. Conventional TURBT (cTURBT) involves the electro-resection of the tumor into small fragments. This technique leads to concerns about the completeness of resection, under-staging, bleeding, cancer cell implantation, and most importantly, risk of tumour recurrence. To circumvent this, laser en-bloc resection of bladder tumors has been introduced.ObjectivesAssessment of the safety, feasibility, and quality of Thulium Laser En-bloc Resection of Tumors (TmL-ERBT) for treatment of Non-Muscle Invasive Bladder Cancer (NMIBC) in various urinary bladder walls as a primary endpoint. The secondary endpoints were to investigate the feasibility of thulium laser use in the re-staging cystoscopy and to evaluate the learning curve of TmL-ERBT.MethodsThis is a prospective observational study including all newly diagnosed patients, above 18 years old, with a urinary bladder mass ≤ 4 cm in maximal dimension (measured via bladder ultrasound or CT or MRI). All patients underwent TmL-ERBT under regional anaesthesia in a lithotomy position. All intraoperative complications such as obturator nerve reflex, bladder perforation, and significant bleeding were recorded. Postoperative variables such as the mean catheterization time, bladder irrigation fluid volume and duration, and the mean of hospital stay as well as the postoperative complications were recorded. All patients were risk stratified and managed according to EUA guidelines then followed by a surveillance regimen per 3 months for 6 months.ResultsThe study included 23 patients with a mean age of 53 ± 15.8 years. While 15 patients (65%) had a single tumor, the rest had multiple tumors, ranging from 2 to 3 in number with a total of 36 lesions. No cases required conversion to cTURBT and none of them experienced obturator nerve reflex or bladder perforation. Only one patient (4.3%) had an attack of clot urine retention. The mean hospitalization time was 31.2 ± 14.4 h and the mean catheterization time was 20.4 ± 13.3 h. The Detrusor muscle was present in 20 patients (87%) and the remaining 3 patients required a re-staging cystoscopy which was performed efficiently using thulium laser. None of the treated patients developed tumour recurrence during the follow-up period. In analysis, the duration of complete resection of 2–4 cm tumours was 23–27 min after the 7th case with a resection rate of 0.12–0.15 cm/min.ConclusionTmL-ERBT is safe and feasible for complete resection of NMIBC with a short learning curve and adequate cancer control.

Evaluation of the efficacy and safety of ultrasound guided injection of carbon nanoparticles as a preoperative localizing tool of non-palpable breast cancer and sentinel lymph nodes detection

Objective This study aimed to measure the efficacy of using carbon nanoparticles in the preoperative localization of early breast cancer (BC) cases as well as in the detection of sentinel lymph nodes in Egypt. In addition, the purpose of the study was to determine whether the efficacy of carbon nanoparticles outweighs their high price and additional shipping fees. Material and methods The current pilot study enrolled 16 early BC patients, particularly those eligible for breast-conserving surgery. All patients underwent standardized injection techniques. The operating surgeons provided comprehensive intraoperative findings and postoperative histopathological reports of the excised tissues. Results After neoadjuvant chemotherapy (NAC), downstaging of the study subjects was achieved until reaching the TNM stage of T1N1M0 and T1N0M0 in 2 cases (12.5%) and 14 cases (87.5%), respectively. Ultrasound-guided injection of carbon nanoparticles was done, followed by surgical excision on the same day or the day after injection. Eleven patients had positive mass lesions preoperatively, with a mean tumoral size of less than 1 cm in maximum dimension. Moreover, 6 out of the 11 patients showed positive black staining intraoperatively with an accuracy of 68.75%. Postoperative histopathological examination (the gold standard) of axillary specimens revealed that 3 out of 16 of the study population have positive tumor-infiltrated lymph nodes. However, only 2 of these cases demonstrated intra-operative black staining, with the black dye’s positive and negative predictive values of staining being 100% and 92.2%, respectively. Conclusions Preoperative carbon nanoparticle suspension injection is a safe and effective method for adequate tumoral localization in BC patients. Nevertheless, this pilot study did not provide strong evidence for the adequacy of sentinel lymph node detection due to the small sample size, high cost, and extra shipping fees of the carbon nanoparticles.

Role of Angular Interface Sign in Characterizing Small Exophytic Renal Masses in Computed Tomography; Prospective Study.

The widespread use of computed tomography (CT) has increased the incidence of small renal cell masses. We aimed to evaluate the usefulness of the angular interface sign (ice cream cone sign) to differentiate a broad spectrum of small renal masses using CT. The prospective study included CT images of patients with exophytic renal masses ≤ 4 cm in maximal dimension. The presence or absence of an angular interface of the renal parenchyma with the deep part of the renal mass was assessed. Correlation with the final pathological diagnosis was performed. The study included 116 patients with renal parenchymal masses of a mean (± SD) diameter of 28 (± 8.8) mm and a mean age of 47.7 (±12.8) years. The final diagnosis showed 101 neoplastic masses [66 renal cell carcinomas (RCC), 29 angiomyolipomas (AML), 3 lymphomas, and 3 oncocytomas] and 15 non-neoplastic masses [11 small abscesses, 2 complicated renal cysts, and 2 granulomas]. Angular interface sign was statistically comparable in neoplastic versus non-neoplastic lesions (37.6% versus 13.3%, respectively, P = 0.065). There was a statistically higher incidence of the sign when comparing benign versus malignant neoplastic masses (56.25 vs. 29%, respectively, P = 0.009). Also, comparing the sign in AML versus RCC was statistically significant (52% of AML versus 29% of RCC, P = 0.032). The angular interface sign seems beneficial in predicting the nature of small renal masses. The sign suggests benign rather than malignant small renal masses.

Primary Pulmonary Hyalinizing Clear Cell Carcinoma: Case Series With Review of Literature.

Background: Hyalinizing clear cell carcinomas of tracheobronchial origin are very rare salivary gland type tumors accounting for less than 1% of lung tumors with only 13 cases reported to date. Their radiological features, morphological spectrum, and molecular features are not well described. Aim: To perform a clinicopathological analysis of primary pulmonary hyalinizing clear cell carcinomas. Method: A retrospective search of primary pulmonary hyalinizing clear cell carcinomas was conducted from authors' institutions and the clinicopathological features including details of molecular testing were analyzed. Results: Five primary pulmonary hyalinizing clear cell carcinomas were identified. The mean patient age at diagnosis was 48.2 years (range: 33-64 years). Three patients were women. All patients were nonsmokers and 3 were symptomatic; 2 were detected incidentally during health screening. The tumors were located in the main lobar bronchi ranging from 1.3 to 4.9 cm in maximum dimension. Microscopy showed cords and nests of at least, focally clear tumor cells. Mucin cysts lacking goblet cells were seen. All tumors were uniformly positive for p40, p63, AE1/AE3, keratin 7, and epithelial membrane antigen but negative for TTF1, KIT, neuroendocrine markers, and other myoepithelial markers. All cases showed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement. Perineural invasion and lymph node metastases were detected in patient 5. Two patients with available follow-up data were recurrence-free until 4 years (patient 1) and 9 months (patient 5) after resection. Conclusion: The present series adds to the scant available literature on primary pulmonary hyalinizing clear cell carcinomas highlighting the characteristic histomorphology, immunoprofiles, and benign outcomes of these rare tumors.

RADT-03. GOLDILOCKS AND THE THREE DOSES OF RADIOSURGERY FOR SMALL BRAIN METASTASES

Abstract INTRODUCTION The optimal dose for single-fraction radiosurgery (SRS) for small brain metastases (BM) (&amp;lt; 2 cm) has not been established considerable variability in dose selection. METHODS Consecutive patients diagnosed with intact BM &amp;lt; 2 cm in maximum dimension treated with SRS to prescription doses of 24, 22, or 20 Gy on the Gamma Knife® between 3/2019-1/2021 were reviewed. Institutional dosing prescriptions were: 24 Gy for &amp;lt; 10 lesions, 22 Gy for 10-20, and 20 Gy for &amp;gt;20). Endpoints included freedom-from-local-failure (FFLF) and radionecrosis on a per-lesion basis calculated from date of SRS to event. Univariable and multivariable analyses were performed using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS 133 patients with 863 BM met inclusion criteria. Prescription dose was 24 Gy for 416 (48.2%) lesions, 22 Gy for 266 (30.8%), and 20 Gy for 181 (21.0%). 20 Gy was associated (all p&amp;lt; 0.001) with younger age, presence of extracranial-disease, progressive extracranial-disease, lung primary, higher number of BM per SRS course (median 17 for 20 Gy, 14 for 22 Gy, 6 for 24 Gy), and smaller per-lesion tumor volume. With a median follow-up of 15 months, 76 (8.8%) LFs occurred. Actuarial 1-year FFLF was 91.2% (95%CI: 88.6-94.8%) for 24 Gy, 92.5% (89.1-95.9%) for 22 Gy, and 77.9% (71.2-84.6%) for 20 Gy (p&amp;lt; 0.001). On multivariable analysis, factors independently associated with adverse FFLF (all p&amp;lt; 0.05) were male sex, presence of extracranial-disease, breast or lung primary, and 20 Gy prescription dose (HR: 2.52, 95%CI: 1.34-4.76). The cumulative 1-year radionecrosis rate was 7.0% for 24 Gy, 4.0% for 22 Gy, and 3.8% for 20 Gy (p=0.035). CONCLUSION For BM &amp;lt; 2 cm, we propose a testable hypothesis that 22 Gy prescription dose may represent the “Goldilocks zone”- superior to 20 Gy regarding LF and superior to 24 Gy concerning radionecrosis.

Analysis of Local Control Outcomes and Clinical Prognostic Factors in Localized Pelvic Ewing Sarcoma Patients Treated with Radiation Therapy: A Report from the Children's Oncology Group

<h3>Purpose/Objective(s)</h3> To identify potential clinical prognostic factors associated with a higher risk of local recurrence in localized pelvic Ewing Sarcoma (ES) patients treated with radiation therapy. <h3>Materials/Methods</h3> Data for 101 patients treated with definitive radiotherapy (RT) or both surgery and radiation (S+RT) on INT-0091, INT-0154, and AEWS0031 were analyzed. Radiation and imaging data was reviewed at IROC QARC. Imaging data for patients who did not receive radiation was not available, so surgery only patients were excluded. Tumor size was classified as </≥ 8 cm in maximum dimension and </≥ 200 mL volumetrically. Pelvic subsites were categorized as sacrum, iliac/buttock, or ischiopubic-acetabulum. Five-year cumulative incidence of local failure was defined as standard. <h3>Results</h3> The most common primary pelvic subsite was sacrum, 44.6%. Median tumor size at diagnosis was 9.7 cm (range: 2.4-16.0 cm) in maximum dimension and 215.9 mL (range: 3.7-1400.0 mL) volumetrically. RT was utilized in 68% of patients and S+RT in 32%. There was no statistically significant difference in local therapy modality employed based on tumor subsite or size. The five-year cumulative incidence of local failure for the entire cohort was 19.0% (95% CI, 12.7-28.5%). RT was associated with a higher incidence of local failure at 25.0% compared to 6.3% for S+RT (p=0.046). There was no difference in local failure outcomes by tumor size </≥ 8 cm in maximum dimension or </≥ 200 mL volumetrically. A higher incidence of local failure was seen with each additional 100 mL of tumor at diagnosis for all patients (p=0.04) and for RT only patients (p=0.005). Tumors originating in the ischiopubic-acetabular region were associated with the highest local failure incidence of 37.5%, compared to 20.0% for iliac-buttock and 11.4% for sacrum (p=0.02). Ischiopubic-acetabulum tumors treated with RT alone had the highest local failure rate in the cohort (50.0%, p=0.06). Multivariable analysis demonstrated RT alone (HR 5.1, p=0.04), tumor subsite (particularly ischiopubic-acetabulum tumors, HR 4.6, p=0.02), and increasing volume per 100 mL (HR 1.2, p=0.01) were associated with a higher incidence of local recurrence. <h3>Conclusion</h3> Patients with pelvic ES selected for S+RT had lower rates of local failure compared to patients selected for definitive RT. Tumors involving the ischiopubic-acetabular region and increasing tumor volume at diagnosis likely correlate with inferior local tumor control outcomes, especially for RT only patients, indicating local therapy intensification may be warranted for this cohort. Tumor characteristics did not correlate with choice of local therapy modality suggesting an opportunity to develop best local therapy practices guidelines for future studies based on tumor features.

Solitary Fibrous Tumor of the Adrenal Gland.

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that can arise at various anatomic locations. It is characterized by inv12(q13q13)-derived NAB2::STAT6 fusion, resulting in the nuclear expression of STAT6. Primary SFT of the adrenal gland is rare. We launched a multi-institutional collaboration to comprehend the overarching demographics, clinical and follow-up, macroscopic, microscopic, IHC, and FISH features of 9 patients with SFT of the adrenal gland. We added a series of 9 patients to the collection of adrenal SFTs where the clinicopathologic parameters, including clinical presentation, imaging, histopathology, IHC, molecular profiles, and management and follow-up data, were analyzed comprehensively. A modified 4-variable risk stratification model, including age, tumor size, and necrosis, was applied. Our series consisted of 6 male and 3 female patients, ranging in age from 19 to 64 years (mean, 49.3 years). Abdominal pain (4) and fever with abdominal pain (1) were the presenting symptoms in 5 patients. In the remaining 4 patients, the tumors were detected by abdominal imaging for hypertension and diabetes. The size of the tumor ranged from 2 cm to 10.5 cm in maximum dimension. All tumors exhibited the morphology of a spindle cell SFT with a patternless architecture; 3 had a focal storiform arrangement. STAT6 positivity was observed in all tumors, and 7 were positive for CD34. Surgical resection was the primary modality of treatment. No adjuvant therapy was administered. Follow-up ranging from 7 months to 23 months was available for 7 patients. All were alive without disease recurrence or metastasis. Risk stratification placed 8 (88.9%) patients into a low-risk category and 1 into an intermediate-risk category. This series is the largest of adrenal SFTs to date. These tumors of the adrenal gland are predominantly spindle cell neoplasms with indolent behavior, with a wide age distribution and a slight male preponderance. Combining our cohort with the previously published cases, the majority of tumors fall into the low-risk category for the propensity to develop metastases. Owing to the rarity and age distribution associated with these tumors, the differential diagnosis is wide and requires a systematic approach for ruling out key differential diagnoses aided by STAT6 IHC.

ALK rearrangement-associated renal cell carcinoma morphologically mimicking mucinous tubular and spindle cell carcinoma: a case report

BackgroundAnaplastic lymphoma kinase rearrangement-associated renal cell carcinoma (ALK-RCC) is an extremely rare tumor and ALK-RCC that mimics mucinous tubular and spindle cell carcinoma (MTSCC) has been very reported only in one instance.Case presentationA 42-year-old Japanese woman was admitted to our hospital for the treatment of a left renal tumor measuring 5 cm in maximum dimension. She underwent a laparoscopic left nephrectomy. Histologically, the tumor formed tubular or focally papillary structures with a small amount of spindle-shaped tumor cells against the background of prominent extracellular mucin. Although the tumor cells were negative for immunohistochemistry (IHC) of alpha-methylacyl-CoA racemase (AMACR) and lymph node metastasis was presented (these are atypical findings for MTSCC), we initially diagnosed the tumor as MTSCC based on its morphological characteristics with mucin deposition. However, an additional IHC analysis revealed that the tumor cells were diffusely positive for ALK-IHC. In addition, TPM3 exon 8 – ALK exon 20 fusion gene was detected by RNA sequencing. The tumor was thus correctly diagnosed as ALK rearrangement-associated renal cell carcinoma (ALK-RCC).ConclusionsSince the use of molecular targeted therapy with an ALK inhibitor for ALK-RCC is promising, the correct pathological diagnosis of ALK-RCC is quite important. We strongly recommend that ALK-IHC be routinely performed for renal tumors with negative AMACR staining that mimic MTSCC.

Wound Complications Following Wide Resection and Intraoperative Radiation Therapy for Management of Soft Tissue Sarcoma of the Extremities

In cases where wide margins are not readily achievable during limb-sparing surgery (LSS) for soft tissue sarcoma (STS) of the extremity, intraoperative radiation therapy (IORT) may be used either alone or in conjunction with post-operative radiation (PORT) to improve local control with potentially decreased toxicities. The aim of this study is to describe wound healing issues following IORT for extremity STS.Retrospective analysis was performed for 92 patients treated with LSS and IORT for definitive management of extremity STS between 2012 and 2020 at a single institution. No patients received pre-operative RT. Major wound complications were classified as follows: secondary operation for wound repair requiring general/regional anesthesia, other invasive procedure for wound management, readmission for wound care, or persistent deep packing over 120 days. Univariate and multivariate binary logistic regression analyses were performed to identify factors associated with development of major wound complications.Median age at IORT was 58 years (IQR 35-71). Tumor distribution was 25% upper extremity and 75% lower extremity. The most common histologies were undifferentiated pleomorphic sarcoma (27%), synovial sarcoma (24%), and liposarcoma (18%). Tumors were grade 1 (14%), grade 2 (34%), and grade 3 (52%). 37% had received pre-operative chemotherapy. Median tumor size at resection was 7 cm (IQR 5-11), and 28% of patients had tumors over 10 cm in maximum dimension. The majority of patients received a prescribed IORT dose of 12 Gy (27%) or 15 Gy (66%). 30% of patients underwent complex surgical closure, as defined by use of a muscle flap (11%, n = 10), fasciocutaneous flap (5%, n = 5), and/or skin graft (16%, n = 15). 90% of patients were discharged in less than 1 week from LSS with IORT. 72% subsequently received PORT at a median time of 7 weeks from LSS (IQR 5-11). Overall, the rate of major wound complications was 18% (n = 17), of which 4 events occurred prior to PORT and 9 events occurred within 4 months from IORT. In total, 10% (n = 9) required a secondary operation for wound repair, 5% (n = 5) required an invasive procedure (commonly drainage of a seroma/hematoma), and 3% (n = 3) required readmission for wound care. None required persistent deep packing. On univariate analysis, factors predicting for development of a major wound complication included current smoking status (HR 15.86, P = 0.02) and complex wound closure (HR 3.32, P = 0.03), both of which remained significant on multivariate analysis. Factors that were not associated with wound complications included age, tumor size, IORT dose, pre-operative chemotherapy, and PORT.Despite the bias of selective use of IORT for more challenging surgical cases, IORT was not associated with increased rates of wound complications as compared to historical reports, and patients were able to transition to the next phase of therapy in a timely manner as part of optimal interdisciplinary management of STS.

Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Intact or Resected Brain Metastases

<h3>Purpose/Objective(s)</h3> Hypofractionated radiosurgery is often used for large brain metastases (BM) not amenable to single fraction radiosurgery, though the ideal dose-fractionation schedule has not been defined. This phase 1 dose escalation study was designed to define the maximum tolerated dose (MTD) of 5 fraction radiosurgery for intact BM or resection cavities ≥ 3cm and < 6cm in maximal dimension. <h3>Materials/Methods</h3> Dose was escalated according to Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients in 8 patient cohorts of 3 patients per cohort and the target highest acceptable dose limiting toxicity (DLT) rate was set at 25%. Enrollment was closed for 4 months in between each cohort. DLT was defined as any acute or late central nervous system CTCAE toxicity grade ≥ 3 considered possibly related to treatment. DLTs assessment extended through 2 years after treatment or was censored at the time of removal from the study or re-irradiation to the treatment site. <h3>Results</h3> Twenty-four patients with 25 target lesions (5 intact BM, 20 resection cavities) were enrolled from October 2012 – February 2021 at the following dose levels with escalation and de-escalation according to EWOC rules: 6 Gy x 5 (level 0, n = 3), 6.5 Gy x 5 (level 1, n = 12), and 7 Gy x 5 (level 2, n = 9). Primary tumor histologies included non-small cell lung cancer (n = 11), esophageal cancer (n = 4), breast cancer (n = 3), melanoma (n = 3), and others (n = 3). The median tumor/cavity size was 18.5cc (range 9.1 - 57.2cc). The median overall follow-up time is 15.6 months (range 0.5 - 81.6) and median DLT assessment follow-up time is 11.5 months (range 0.5 - 27.3). Four DLTs including intracranial hemorrhage (1) and seizure (3) were observe after a median time of 11 months (range 1-14) in 3/9 patients at dose level 2 and 1/12 patients at dose level 1. Two deaths without clear cause in patients with known DLT were considered possibly related to treatment. Symptomatic RN occurred in 4/9 patients at dose level 2, and 2/12 patients at dose level 1. One patient experienced local tumor failure at 36 months. <h3>Conclusion</h3> The 6.5 Gy x 5 fractions is the maximum tolerated dose and recommended phase 2 dose of 5 fraction radiosurgery for large intact or resected brain metastases. This dose level is well tolerated and local control appears promising, though larger studies are required to further assess treatment efficacy at this dose level.