MPC-7 Clinical features of Diffuse hemispheric glioma, H3 G34-mutant in children and young adults

INTRODUCTION: H3F3A G34R/V mutated gliomas are seen predominantly in children and young adults, and have been proposed as “Diffuse hemispheric glioma, H3 G34-mutant” in cIMPACT-NOW Update 6. However, the clinical features of the tumor have not been fully elucidated. METHODS: We retrospectively reviewed 4 cases with H3G34R mutation among 40 cases diagnosed as glioblastoma under 30 years old or primitive neuroectodermal tumor (PNET) in our hospital. RESULTS: There were one male and three female patients with a median age of 21.5 years (range: 17–27 years). All lesions were localized in the cerebral hemispheres, and the initial symptoms were headache in two cases and seizures in two cases. On imaging, there was one case with poor contrast, and unlike the infiltrative growth pattern of the other three contrasted cases, it showed a well-defined mass lesion. DWI showed high signal in all four cases, reflecting the high cell density in histopathology. All cases were IDH-wildtype. CONCLUSION: Although the patient background and genetic characteristics of the glioma with H3 G34R/V mutation at our institution were generally consistent with previous reports, there were some cases with atypical imaging findings. Further investigation is required for a deeper understanding of the clinical features of this tumor.

Florid Mesothelial Hyperplasia Associated with Abdominal Wall Endometriosis Mimicking Invasive Carcinoma

Florid mesothelial hyperplasia typically occurs in the pelvis, abdomen, or chest associated with an underlying neoplastic or inflammatory process. These lesions are of clinical significance because they can mimic a neoplasm. Early reports were published in the 1970s, but only a few case series of such lesions have been published in the gynecologic pathology literature. Here, we report a case of florid mesothelial hyperplasia with an infiltrative growth pattern, mimicking an invasive carcinoma. The lesion was associated with endometriosis forming a mass lesion in the abdominal wall. Histologically, tubular arrangements and nests of mesothelial cells, some with artifactual slit-like spaces, formed a stellate lesion adjacent to endometrial glands and stroma. Cytologic atypia was mild and reactive, and positive immunostaining for calretinin, WT-1, and cytokeratin 5 identified the lesion as mesothelial and benign. We describe in detail the histologic findings in this case and review the pertinent literature. We discuss the clinically importance of this diagnostic pitfall and the path to arriving at the correct diagnosis.

Oncological Outcomes in Patients with Appendicular Myxofibrosarcomas: A Retrospective Study

Background. Myxofibrosarcoma (MFS) is notorious for its infiltrative growth pattern, making wide excisions difficult to achieve. Our objective was to assess the impact of surgical margins and other factors that affected rates of local recurrence (LR), distant metastasis (DM), and overall survival (OS) of individuals undergoing resection for MFS. Methods. We retrospectively reviewed the medical records of 209 patients with appendicular soft tissue sarcomas between January 2012 and June 2018. Of these, 29 patients (14%) were diagnosed with myxofibrosarcoma. These patients underwent a total of 33 resections. The pathological analyses were conducted by an experienced musculoskeletal (MSK) pathologist. Demographics data, operative details, adjuvant therapy, and oncological outcomes were assessed. Results. Of the 29 patients (33 resections), the overall LR rate was 24% (7/29) and the 2-year LR rate was 17% (5/29). Factors associated with negative oncological outcomes were as follows: tumor size ≤10 cm (2-year local recurrence-free rates (LRFRs), 65%; 95% CI, 44–86%; p = 0.02 ) and positive surgical margins grouped with surgical margins ≤0.1 cm (hazard ratio (HR), 11.74; 95% CI, 1.41–97.74; p = 0.02 ). Chemotherapy and radiotherapy together increased the 2-year LRFR (LRFR, 100%; 95% CI, 100%, p = 0.001 ). Two-year DM and OS rates were 15% and 79%, respectively. Female gender was a predictor of distant metastasis. Local recurrence had a negative impact on overall survival. Intraoperative analysis of resection margin accuracy was 75% (12/16) when non-MSK pathologists were involved but 100% accurate (12/12) when analyzed by an MSK pathologist. Conclusion. Myxofibrosarcomas showed high LR rates after treatment. Close margins (≤0.1 cm) should be considered as a risk factor for LR, and LR is associated with negative overall survival. Neoadjuvant therapy in terms of combined chemotherapy and radiation therapy associates with decreased LR rates. If intraoperative assessment of margins is to be done, it should be performed by an experienced MSK pathologist.

OS05.7.A Absence of severe hematological toxicity during first line treatment predicts low chance on severe toxicity during second line alkylating chemotherapy in glioblastoma

BACKGROUND Glioblastoma has an infiltrative growth pattern that makes complete resection of the tumor virtually impossible. Sooner or later the tumor progresses, even after aggressive treatment with maximal safe resection, radiotherapy and/or chemotherapy. Hematological toxicity is an important cause of treatment delays during 1st line treatment. How often hematological toxicity occurs during 2nd line treatment is unclear. We explored rates of hematological toxicities in patients treated with temozolomide or lomustine at progression and investigated the association between severe toxicity during 1st and 2nd line treatment. METHODS We studied a retrospective cohort study of adult patients (n=247) with a glioblastoma treated with 2nd line alkylating chemotherapy at the Brain Tumor Center Amsterdam between 2000 and 2020. First line treatment of these patients consisted of a combination of radiotherapy combined with different treatments (80% received temozolomide, 4% PCV, 6% other chemotherapy and 10% radiotherapy only). Second line treatment consisted of temozolomide or lomustine. Mild and severe hematological toxicity were defined according to the CTCAE (version 5.0) criteria as a grade 1&2 and grade ≥3, respectively. We used descriptive statistics to analyze frequencies of hematological toxicity in patients with glioblastoma treated with 2nd line chemotherapy. RESULTS Sixty percent (147/247) of patients treated with 2nd line chemotherapy experienced hematological toxicity (grade 1–4). Considering subtypes of hematological toxicities, more patients experienced hematological toxicity during 2nd line treatment; severe thrombocytopenia occurred most frequently observed (6,1 during 1st line vs. 10,5% during 2nd line treatment), followed by neutropenia (3,6 vs. 6,9%), leukocytopenia (4,0 vs. 5,3%) and anemia (0 vs. 0,8%). Fewer patients treated with 2nd line temozolomide (n=113) experienced mild and severe hematological toxicity than patients treated with 2nd line lomustine (n=134; 46% versus 71% (for mild) and 12% vs 21% (severe toxicity), respectively). A subset of 107 patients was initially treated with radiotherapy and concurrent and adjuvant temozolomide; within this subset, patients with none or only mild toxicity during 1st line treatment had only a small risk of severe hematological toxicity during 2nd line treatment (4%). In contrast, the 34,5 % of patients with severe hematological toxicity during 1st line treatment also experienced severe hematological toxicity during 2nd line alkylating chemotherapy. CONCLUSION Hematological toxicity occurs more frequently during 2nd line treatment. Treatment with 2nd line temozolomide results in less hematological toxicity than lomustine. Absence of severe toxicity during 1st line treatment is predictive for the risk of toxicity during 2nd line treatment.

Polymorphous Adenocarcinoma of Lacrimal Gland: A Rare Case Report

Polymorphous adenocarcinoma is a slow growing malignant tumor of minor salivary glands. The most common location of these tumors is palate, buccal mucosa, upper lip, floor of mouth and retromolar region. This malignant neoplasm is characterized by cytological uniformity, architectural diversity and infiltrative growth pattern. This is a case report of polymorphous adenocarcinoma occurring in lacrimal gland. They are seldom reported in this location and propose unique diagnostic challenges.

What’s behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns

Purpose Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68Ga-PSMA-11-PET examinations. Methods RPE specimens of 62 patients with preoperative 68Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA%neg) were correlated with spatially corresponding SUVmax on 68Ga-PSMA-11-PET in a multidisciplinary analysis. Results All tumours showed medium to strong membranous (2–3 +) and weak to strong cytoplasmic (1–3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA%neg. PSMA%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA%neg (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan. Conclusions We describe PSMA%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.

What's behind 68Ga-PSMA-11 Uptake in Primary Prostate Cancer PET? Investigation of Histopathological Parameters and Immunohistochemical PSMA Expression Patterns.

Purpose: Prostate specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding 68Ga-PSMA-11-PET examinations.Methods: RPE specimen of 62 patients with preoperative 68Ga-PSMA-11-PET between 2016 and 2018 were analyzed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunhistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA%neg) were correlated with spatially corresponding SUVmax on 68Ga-PSMA-11-PET in a multidisciplinary analysis.Results: All tumours showed medium to strong membranous (2-3+) and weak to strong cytoplasmic (1-3+) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA%neg. PSMA%neg, infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA%neg as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA%neg (p<0.01, OR=9.629) and growth pattern (p=0.0497, OR=306.537) as significant predictors for a negative PSMA-PET scan.Conclusions: We describe PSMA%neg, infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower 68Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.

Convection Enhanced Delivery in the Setting of High-Grade Gliomas

Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood–brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

The First Case Report of a Rare Gastric Plexiform Fibromyxoma: Histological Images With an Infiltrative Growth Pattern of Diffuse Infiltration in Stomach.

Background: Plexiform Fibromyxoma (PF) of the stomach is a very rare mesenchymal tumor of the gastrointestinal tract. We report the first case of PF which was confirmed after surgical resection pathologically. Case summary: The tumor was characterised microscopically infiltrative and diffuse growth into the smooth muscle bundles of the muscularis propria by multinodular and plexiform within myxoid stroma. Immunohistochemistry analysis revealed that the tumor cells were positive or weakly positive for smooth muscle actin (SMA), vimentin and H-caldesmon, and negative for desmin, CD117, CD34, CK-20, Pan-CK, Dog1, S100, ER, PR, and CD10. No mutations of C-kit and platelet-derived growth factor receptor alpha (PDGFRA) were detected in our case. No genetic disruption of glioma-associated oncogene homolog 1 (GLI1) was detected by fluorescence in situ hybridization (FISH). Conclusion: So we mainly relied on the morphological and immunohistochemistry findings and made the final diagnosis of PF.

Convection Enhanced Delivery in the Setting of High-Grade Gliomas

Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.