Biopsy Cases Research Articles

Proliferative Verrucous Leukoplakia: An Expert Consensus Guideline for Standardized Assessment and Reporting

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Fivenon-PVL histologic mimicswere included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as "corrugated ortho(para)hyperkeratotic lesion, not reactive" and "SCC" (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the "Bulky hyperkeratotic epithelial proliferation, not reactive" category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) "corrugated ortho(para)hyperkeratotic lesion, not reactive;" (2) "bulky hyperkeratotic epithelial proliferation, not reactive;" and (3) "suspicious for," or "squamous cell carcinoma." Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

Nephrotic syndrome with focal segmental glomerular lesions unclassified by Columbia classification; Pathology and clinical implication.

BackgroundThe Columbia classification is widely used for diagnosis of focal segmental glomerulosclerosis (FSGS). In practice, we occasionally encounter segmental glomerular lesions unclassified as Columbia classification. We analyzed the clinical implication of unclassified segmental lesions comparing with Columbia-classified FSGS.MethodsA retrospective cohort study from 13 local hospitals in Japan. From 172 biopsy cases diagnosed with FSGS or minimal change disease (MCD)/FSGS spectrum with unclassified segmental lesions, adult patients with nephrotic syndrome who received immunosuppressive therapies were included. The cases are classified by pathology, i.e., typical FSGS lesions sufficiently classified into subgroups of Columbia classification: collapsing (COL), tip (TIP), cellular (CEL), perihilar (PH), and not otherwise specified (NOS), and unclassified by the Columbia classification into three subgroups: “endothelial damage,”; “simple attachment,”; and “minor cellular lesion,”. The response to immunosuppressive treatment and 30% decline of eGFR were compared.ResultsAmong 48 eligible cases, all were Japanese, 34 were typical FSGS; 13 TIP, 15 CEL, 6 NOS, and no COL or PH cases. Fourteen were unclassified cases: endothelial damage (n = 6), simple attachment (n = 5), and minor cellular lesion (n = 3). The median age of overall patients was 60 years old and the median of eGFR and urinary protein creatinine ratio was 51.5 mL/min/1.73m2 and 7.35, respectively. They received similar therapeutic regimen. Kaplan-Meier analysis revealed no significant difference in treatment response between typical FSGS and unclassified cases. Evaluating among the subgroups, endothelial damage, simple attachment and minor cellular lesion showed similar treatment response to TIP or CEL. No significant difference was also observed in the 30% decline of eGFR.ConclusionsJapanese adult patients with nephrotic syndrome showing unclassified segmental lesions as Columbia classification may be equivalent clinical impact as Columbia classification of FSGS.

E-cadherin immunohistochemical expression in gastric carcinoma in relation to different clinicopathological parameters

Background Gastric cancer (GC) is an aggressive malignancy and a common cause of cancer-related deaths worldwide. E-cadherin is a transmembrane calcium-dependent epithelial cell adhesion molecule. Loss of E-cadherin-mediated cell–cell adhesion is needed for tumor cell invasion and metastasis. Cells with mutated E-cadherin demonstrate increased motility, show altered organization of their actin cytoskeleton, and are associated with metastases, thereby providing evidence for its role as an invasion suppressor. Objectives To assess the prognostic value of E-cadherin expression in GC and to evaluate its correlations with other prognostic parameters. Materials and methods Immunohistochemical E-cadherin expression was studied in 36 cases of GC (24 cases of endoscopic biopsies and 12 cases of total gastrectomy), and the results were correlated with clinicopathological parameters. Results E-cadherin was positive in 15/36 (41.7%) cases of GC. A significant inverse correlation was found between E-cadherin expression and tumor grade, number of lymph nodes involved by metastasis, and Helicobacter pylori positivity, with P values of 0.02, 0.04, and 0.03, respectively. Conclusion E-cadherin loss plays an important role in invasion and metastasis potential in GC, and decrease or loss of its expression is predictive of poor prognosis. H. pylori plays an important role in gastric carcinogenesis, and it induces a statistically significant decrease in E-cadherin expression, so eradication of H. pylori infection can stop or decrease the progression of carcinogenesis.

Diagnostic accuracy of combined MUC5A, S100P, and von Hippel-Lindau in differentiating intrahepatic cholangiocarcinoma from metastatic pancreaticobiliary carcinomas presented as hepatic focal lesions

Background Sometimes differentiation between intrahepatic cholangiocarcinoma (ICC) and metastatic pancreaticobiliary carcinoma (mPBC) could be challenging, and it is of great importance owing to different treatment modalities. We aimed to measure the diagnostic accuracy of MUC5A, von Hippel-Lindau (VHL), and S100p in differentiating ICC from mPBC in hepatic focal lesions. Patients and methods The study included 70 cases of liver biopsies presented as hepatic focal lesions divided into two groups: group 1: 40 cases of mPBC and group 2: 30 cases of ICC. Results There was a highly statistically significant difference regarding MUC5A, S100P, and VHL expression between both groups (P&lt;0.001). mPBC showed MUC5A in 87.5%, S100P in 95%, and VHL in 5%. However, cases of ICC showed positive MUC5A in 10%, S100P in 29.6%, and VHL in 80%. Regarding the validity of diagnosing mPBC, S100P had the highest sensitivity (95%), whereas both panels of (MUC5A−/S100P+/VHL−) and (MUC5A+/S100P+/VHL−) showed the highest specificity and positive predictive values (100%). Regarding the validity for diagnosing ICC, VHL had the highest sensitivity (80%), whereas (MUC5A−/S100P−/VHL+) showed the highest specificity and positive predictive value (100%). Conclusion These results indicate the validity of combined MUC5A, S100P, and VHL as a highly sensitive and specific panel for differentiating ICC from mPBC.

Neuroinflammation: 2021 update.

Key requirements for the validity of a neuropathological study are the inclusion of large numbers of biopsy or autopsy cases and proper controls, the rigorous classification of the basic neuropathology and the selection of the most suitable technologies for investigation. Whether the studies are performed with the fanciest, new, and state of the art technology or with rather conventional methodology is of minor importance. Following these criteria, a spectrum of neuropathological studies has been published in 2020, which provides new insights on important questions related to neurological disease. They include the pathological substrate of brain disease in COVID-19 infected patients, the nature of the adaptive and innate inflammatory response, or the type and mechanisms of tissue injury and repair in multiple sclerosis, and diagnostically relevant or mechanistic new insights into antibody-mediated diseases of the central nervous system. Other studies describe in detail the dynamic changes of brain inflammation in patients with trisomy 21 as a disease model for Alzheimer's disease, or the presence and consequences of vascular comorbidities in a chronic inflammatory disease, such as multiple sclerosis. All these contributions have provided important, highly relevant clues for basic and translational neuroscience.

Prevalence of genotype-specific human papillomavirus in cytology specimens and cervical biopsies, and its implication in cervical cancer risk stratification: a retrospective study of 10647 cases.

Objective: This study aimed to describe the risk stratification of squamous cell carcinoma (SCC) and its precursor lesions based on HPV E6/E7 mRNA genotyping.Methods: 10647 hrHPV+ women (mean age 40.8 years), who had concurrent cytology and follow-up biopsy results available between September 2016 and May 2020, met the inclusion criteria and were selected for immediate risk analysis.Results: In this cohort, HPV-16 or 18/45+ women had significantly higher immediate risk of cervical cancer and precancer compared with other genotypes+ women. The relative immediate risk (RIR) of ASC-H+ was 2.0 (95% CI: 1.9-2.4) and SCC was 9.4 (95% CI: 5.5-15.6) for HPV-16 or 18/45+ women when compared with women positive for other 11 genotypes. Among follow-up biopsy cases, the RIR of CIN2+ was 2.7 (95% CI: 3.0-3.7) and SCC was 10.8 (95% CI: 7.2-17.4) for HPV-16 or 18/45+ women than women positive for other genotypes. Similarly, when compared with women positive for other genotypes, the RIR of CIN2+ was 2.9 (95% CI: 2.7-4.6) and SCC was 13.8 (95% CI: 3.0-66.2) for HPV-16 or 18/45+ women with ASC-US, and RIR of CIN2+ was 3.3 (95% CI: 3.1-4.6) and SCC was 22.3 (95% CI: 2.8-176.8) for HPV-16 or 18/45+ women with NILM.Conclusions: This study supports that hrHPV mRNA genotyping can be an effective risk stratification tool to identify individual at higher risk for cervical cancer or precancer, and provides important evidences for the future modifications for current China cervical cancer screening guidelines.

A Diagnostic Biomarker Model Associated with Immune Infiltration in Patients with Antibody-Mediated Rejection after Kidney Transplantation

Background: In spite of advances in development and application of immunosuppressive agents, the long-term survival of grafts still needs to be advanced caused by antibody-mediated rejection (ABMR). Many researchers have paid attention to this area. However, little was known about the role of genes and immune cells in the development of ABMR. Methods: In total, 2533 biopsy cases from four different cohorts were collected. Three Gene Expression Omnibus (GEO) datasets (GSE36059, GSE98320 and GSE12403) were used as the training set, and one GEO dataset and twenty biopsy samples from our center were used for validation. The potential diagnostic prediction value of the signature and immune profiles were also explored. Findings: The LASSO regression model and PPI network were performed to search candidate biomarkers. LAPTM5, GBP2, CCL5 and KLRD1 were obtained as diagnostic biomarkers (AUC = 0·934, 95% CI 0·923-0·943). Immune cell infiltration analysis revealed that γδ T cells which could secrete IL-17A were most related with four biomarkers. The infiltration of γδ T cells and IL-17A were significantly higher in ABMR group than that in ST group. Interpretation: We have identified and established a diagnostic model containing four transcripts as diagnostic biomarkers of ABMR following kidney transplantation. Several types of immune cells were inferred to be involved in the process of ABMR. Among these, γδ T cells were most related with four biomarkers, which may promote ABMR by producing IL-17A. Funding: This work was supported by the National Natural Science Foundation of China [grant numbers 82070769, 81900684, 81870512, 81770751, 81570676, 81470981, 81100532], Project of Jiangsu Province for Important Medical Talent [grant number ZDRCA2016025], the “333 High Level Talents Project” in Jiangsu Province [grant numbers BRA2017532, BRA2016514, BRA2015469], the Standardized Diagnosis and Treatment Research Program of Key Diseases in Jiangsu Province [grant number BE2016791], the Open Project Program of Health Department of Jiangsu Province [grant number JSY-2-2016-099], Jiangsu Province Natural Science Foundation Program [grant number BK20191063]. Declaration of Interest: None to declare. Ethical Approval: This study was approved by the local ethics committee of the First Affiliated Hospital of Nanjing Medical University (2016-SR-029).

Remote Reporting from Home for Primary Diagnosis in Surgical Pathology: A Tertiary Oncology Center Experience during the COVID-19 Pandemic

Background: The COVID-19 pandemic accelerated the widespread adoption of digital pathology (DP) for primary diagnosis in surgical pathology. This paradigm shift is likely to influence how we function routinely in the postpandemic era. We present learnings from early adoption of DP for a live digital sign-out from home in a risk-mitigated environment. Materials and Methods: We aimed to validate DP for remote reporting from home in a real-time environment and evaluate the parameters influencing the efficiency of a digital workflow. Eighteen pathologists prospectively validated DP for remote use on 567 biopsy cases including 616 individual parts from 7 subspecialties over a duration from March 21, 2020, to June 30, 2020. The slides were digitized using Roche Ventana DP200 whole-slide scanner and reported from respective homes in a risk-mitigated environment. Results: Following re-review of glass slides, there was no major discordance and 1.2% (n = 7/567) minor discordance. The deferral rate was 4.5%. All pathologists reported from their respective homes from laptops with an average network speed of 20 megabits per second. Conclusion: We successfully validated and adopted a digital workflow for remote reporting with available resources and were able to provide our patients, an undisrupted access to subspecialty expertise during these unprecedented times.

Profile of Skin Biopsies and Patterns of Granulomatous Skin Diseases in a Tertiary Care Center of Western Nepal

Background: Granulomatous skin diseases are one of the leading causes of morbidity in tropical countries like Nepal. These granulomatous skin lesions often pose diagnostic challenge to clinicians as well as to dermatopathologists. Histopathologic examination of a biopsy specimen represents one of the most informative and cost-effective procedure and may help to avoid other, costlier and invasive diagnostic workup. &#x0D; Materials and Methods: This cross-sectional observational study from October 2018 to October 2019, at department of dermatology, enrolled 142 cases of skin biopsies. Correlation between clinical impression and histopathological findings was evaluated. &#x0D; Results: Out of 13940 dermatology visits/ consultations, 142 (1.01%) skin biopsies were performed. Head, neck and face were the commonest sites of biopsies (29.6%). The most common biopsy technique was incisional type in 70 (50.4%). Histopathology showed granulomatous features in 49 (34.8%) cases, out of which tuberculoid type was the commonest, in 29 (58.0%). Positive clinicopathological correlation was seen in 117/142 (82.4%) for all biopsies and 41/49 (85%) for granulomaous skin lesions. &#x0D; Conclusion: Tuberculoid type was the most common cutaneous granuloma. High clinicopathological correlation in our study supports histopathology as an important tool for diagnosis of granulomatous as well overall skin disorders.

Effect of Thymus vulgaris oil on the growth of Helicobacter pylori

Man has used medicinal plants for a long time. Among these Thymus vulgaris whose therapeutic virtues have been proven by many works, especially in the field of the fight against infectious diseases. The objective of this work is to evaluate the effect of essential oils, obtained by extraction from a medicinal plant Thymus vulgaris on the growth of Helicobecter Pylori. Various pro-cesses for extracting T. vulgaris essential oil from the Tessala region of SBA (Western Algerian) have been highlighted. Quantitative analysis of T. vulgaris essential oil after its hydrodistillation extraction showed a good yield of 3.2%.The study of the antibacterial effect of T. vulgaris essential oil against the H. pylori taken from gastric biopsies (cases of gastritis, ulcer, malignant tumor) within the Gastroenterology Department at the Hospital University Centre of SBA, was highlighted by the aromatogram test, the MIC and MBC test and the test of monitoring bacterial growth in the absence and presence of essential oil. The aromatogram test of H. pylori in the presence of T. vulgaris essential oil allowed us to test several inhibitory concentrations (10-1 to 10-5). The results of the aromatogram obtained showed a good activity of T. vulgaris essential oil in comparison with H. pylori. In all the three pathological cases (gastric malignant tumours, gastritis and ulcer). The results of the MIC and MBC tests allowed us to determine the minimum inhibitory concen-tration and that of bactericidal, whose highest recorded inhibition values of T. vulgaris essential oil in relation to H. pylori in all the three above stated pathological cases are (62.5, 125) μ.ml-1respectively.

A Clinico-Histopathological Correlative Study of Non-Infectious and Erythematous Papulosquamous Lesions of Skin in a Tertiary Care Hospital

Context: Papulosquamous lesions of skin are the most frequently seen conditions encountered by both dermatologists and pathologists. These conditions have a similar clinical picture; hence a definite histopathological diagnosis can solve the overlapping clinical features of various papulosquamous lesions of skin. Aims: To study the histopathological features of various subcategories of papulosquamous skin lesions and to assess the correlation between clinical diagnosis provided and the histopathological diagnosis obtained. Settings and Design: The study is done in a Tertiary care hospital which includes 150 skin biopsies received from Department of Dermatology. Methods and Material: The skin biopsy specimens were subjected to formalin fixation and paraffin embedding followed by staining with hematoxylin and eosin. The histopathological features of various papulosquamous lesions were analysed and clinicopathological correlation was done for the 150 cases of skin biopsies which were clinically suspected/ diagnosed as papulosquamous skin lesions. Statistical analysis used: Universal sampling done and this is a clinico-histopathological correlative study done for a period of 18 months. Results: Out of the 150 skin biopsies of papulosquamous lesions, psoriasis turned out to be the most common lesion. The papulosquamous skin lesions were commonly seen in males. 28% cases were of psoriasis vulgaris and 25% cases were of Lichen planus occupying the top two commonest papulosquamous skin lesions and a positive correlation with histopathological diagnosis turned out to be 76%. Conclusions: The complexity in diagnosing papulosquamous lesions due to features of clinical overlap can be overcome by the histopathological examination and findings which helps to diagnose the various subcategories of papulosquamous skin lesions.

Demographic and morphological analysis of granulomatous dermatoses

Introduction: Granulomatous reaction is chronic inflammatory pattern which is characterized by presence of granulomas. Many of the skin granulomatous conditions produce identical pattern and hence it remains always a diagnostic challenge to pathologist. Arrival at the accurate diagnosis is of great interest so that appropriate treatment can be ensured. Aim: To study different morphological patterns of granulomatous lesions of the skin along with the etiology and demographic pattern. Materials and Methods: All the skin biopsies with the histological features of granulomatous disease received in the Pathology Department, Father Muller Medical College for a period of three and half years (Jan 2009 to May 2012) are included in the study. The clinical details and H and E sections of all the cases were reviewed. Results: Of 75 cases of skin biopsies with granulomatous lesions, 65 (85%) were found in males. Out of these, Tuberculoid type of granulomas was seen in 57 cases (76%), suppurative type in 10 cases (13.4%), Necrobiotic type in 4(5.3%) cases and foreign body type in 4(5.3%) cases. Sixty five cases (86%) were infectious granulomatous lesions. Leprosy was amounting to 49 cases (65%), followed by tuberculosis and chromoblastomycosis with each of 8 cases. Other causes were foriegn body granuloma, necrobiosis lipoidica and granuloma annulare. Conclusion: Males are more commonly affected by granulomatous dermatosis. In this study, tuberculoid granulomas were the most common type. The most common cause of granulomatous skin lesion was leprosy. Other common cases were tuberculosis and chromoblastomycosis. Keywords: Granulomatous, Skin, Morphology, Etiology.

Spectrum of Endometrial lesions in patients presenting with abnormal uterine bleeding

Introduction: Most of the patients with bleeding per vaginum undergo either colposcopic evaluation or Pap smear for cervical pathology or Trans Vaginal Ultrasound and endometrial biopsy to diagnose the definite pathology affecting endometrium. This study was done to see the pattern of histopathological spectrum of endometrial biopsy and their clinical correlation in a tertiary care hospital. Materials and Methods: This was a retro-prospective study conducted at a tertiary care hospital in western Maharashtra. 1000 biopsy cases were studied. Light microscopy examination and clinical diagnoses were correlated. Results: out of 1000 patient’s maximum number belonged to perimenopausal age group followed by reproductive age group and then postmenopausal age group. In 483 cases normal histopathological pattern was observed, out of which 259 cases showed proliferative phase endometrium (25.9%) and 224 cases showed secretory phase (22.4%). 104 cases showed simple (10.4%) and 43 cases (4.3%) complex hyperplasia. Exogenous hormonal effect was seen in 148 cases (14.8%). The least pattern which was observed was endometrial carcinoma, seen in only 2.3% of patients. Conclusion: The study showed that carcinoma was most common in the post-menopausal age group. This group also had the maximum frequency of atrophic endometrium and complex hyperplasia. Proliferative endometrium was recorded highest in perimenopausal age group while reproductive age group showed highest frequency of secretory type endometrium. This study is in concordance with most other conducted studies on similar parameters. Keywords: Biopsy, Endometrium, Uterine bleeding.

Granulomatosis With Polyangiitis in a Pediatric Male

Significant eosinophilia is a prominent feature in Churg-Strauss syndrome but has not been described in granulomatosis with polyangiitis (GPA) in a pediatric patient. We present a biopsy case that confirmed granulomatosis with polyangiitis with significant eosinophilia > 30% on the initial presentation. Etiologies that could account for eosinophilia were excluded during workup. The patient's presentation of pulmonary alveolar hemorrhage, conjunctivitis arthritis, high-titer cytoplasmic antineutrophil, PR3-ANCA antibodies, and cytoplasmic antibodies (cANCA) was consistent with a clinical picture of atypical GPA in a pediatric patient. This case presents a rare opportunity not only due to GPA’s low incidence in the pediatric population but due to the unusual nature of significant eosinophilia in GPA.

LGG-32. CLINICAL OUTCOME OF PEDIATRIC GLIOMAS IN SINGLE INSTITUTION

Gliomas in children are rarer than in adult, then treatment strategies might vary from facility to facility. We report clinical features and outcome of pediatric glioma in our institution. Twenty-nine patients diagnosed with glioma, exclude ependymoma, 14 boys and 15 girls, among 98 pediatric brain tumor patients treated at Kagoshima University Hospital since 2006 were reviewed histopathology, extent of resection, adjuvant therapy and outcome, etc. Mean age at surgery was 10.4 (S.D. 5.6) years. Median follow-up period was 19.1 months. Histopathological diagnosis comprised 8 pilocytic astrocytoma, 3 ganglioglioma, 2 subependymal giant cell astrocytoma, 5 WHO grade Ⅱ astrocytoma, 8 glioblastoma, and desmoplastic infantile astrocytoma, anaplastic astrocytoma and astroblastoma were one case each. Tumor resection was performed in 24 cases, and 5 cases underwent biopsy. Chemotherapy was performed in 15 cases and irradiation was performed in 9 cases. Out of 5 WHO grade Ⅱ astrocytoma cases, 2 cases underwent biopsy following chemotherapy, 1 case underwent biopsy only and other 1 case underwent total resection. The four cases show long survival ranged from 71 to 136 months without irradiation. All of eight glioblastoma cases show poor prognosis ranged from 8.6 to 26.7 months regardless of chemo-radiotherapy. In management for pediatric brain tumor patients, irradiation is often laid over until recurrence. In WHO grade Ⅱ astrocytoma, the treatment strategy might be reasonable using appropriate chemotherapy even though biopsy cases.

GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM

BACKGROUNDWe integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.METHODSData from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews.RESULTSAll but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.CONCLUSIONSThese in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

ES-1 Clinical results of tumor treating fields in patients with glioblastoma in Japan, compared with global surveillance

INTRODUCTION: The tumor treatment field induces apoptosis of tumor cells by providing a low intensity, intermediate frequency, alternating current electric field via a transducer array. TTFields is based on Phase 3 EF-11 and EF-14 trials for glioblastoma in the US FDA and Japan PMDA. Therefore, I will report the statistics of TTFields use in Japan along with recent papers. METHODS: 410 patients were treated with TTFields in Japan (December 2017-), of which 17 were at Tokyo Women’s Medical University. We also referred to papers about global post-marketing surveillance and recent studies. RESULTS: Of the 410 patients, 409 (99.8%) were diagnosed with ndGBM(male: female, 66.8%: 33.2%). As of June 2020, 222 patients (54.1%) were on treatment and 188 (45.9%) were discontinued. In 17 cases at TWMU, the average age was 46.3 years. The average treatment period was 218 days, with 6 patients (35%) continuing treatment, 6 patients (35%) discontinuing due to patient wishes, and 5 patients (30%) discontinuing treatment due to recurrence. Side effects were contact dermatitis under the array in 9 patients (57%) and mild malaise in 7 patients (43%). We experienced long-term progression-free cases with TTF use of 25 months (survival 30 months after surgery) with a glioma partially resected and 21 months (survival 27 months after surgery) with a biopsied glioma. In the biopsy case, bevacizumab was used in combination during the treatment. Conclusion: In global surveillance, use for rGBM accounts for 39%, but Japan is limited to use for ndGBM due to insurance coverage. In terms of side effects, it showed a good safety profile comparable to previous trials. Long-term progression-free cases have been observed, and it is necessary to examine the characteristics of patients who respond to treatment and the effect of concomitant use with bevacizumab by prospective studies

18227 Side effect: Characterizing laterality and site-specific patterns in lentigo maligna and lentigo maigna melanoma on the human body

Melanoma is known to have a left-sided laterality, yet few studies have examined the anatomic variations in the subtypes lentigo maligna (LM) and lentigo maligna melanoma (LMM). Here we aimed to examine laterality and anatomic distribution of LM and LMM at a single university center. A total of 392 biopsy cases (241 LM and 151 LMM) from 2008 to 2018 were included in this study. Chi-square tests were used to evaluate LM/LMM based on gender, body site, laterality, and metastasis. Analysis of variance models were used to compare Breslow depth. There was no overall statistically significant laterality (left 54.5% vs right 45.5%, P = .0890), however, there was a significant increase in left-sided LM/LMM on the head/neck (left 59.1% vs right 40.9%, P = .0178). LM/LMM showed the following frequencies per body site: head/neck 49.7%, upper limbs 25.3%, trunk 16.8%, and lower limbs 8.3%. Men demonstrated a higher incidence of LM/LMM on the head/neck and trunk (head/neck men 58.2% vs women 35.0%, trunk 18.9% men vs 13.3% women, P < .0001), while women showed a higher incidence on extremities (upper limbs men 20.5% vs women 33.6%, lower limbs men 2.4% vs women 18.2%, P < .0001). There was a significant increase in metastasis on the upper limbs (LMM:LM ratio 1.11 upper limbs; P = .0018) and on the right side of the female body (LMM:LM ratio 1.36 right; P = .0257). Overall, LM/LMM does not share left-sided laterality patterns with melanoma, except when on the head/neck. Like melanoma, LM/LMM is commonly found on the head/neck and upper extremities. These findings may aid in diagnosis of LM/LMM.

ML-01 Pathological characteristics of primary central nervous system lymphoma with atypical radiological finding

Background: If the brain tumor is suspected to be a primary central nervous system lymphoma (PCNSL) on radiological findings, it is general to perform biopsy to obtain the pathological diagnosis. Glioblastomas (GBs) must be distinguished from PCNSLs. In addition to commonly used contrast-enhanced T1-weighted imaging, diffusion-weighted image (DWI), and apparent diffusion coefficient (ADC) value, the following characteristics of PCNSLs were reported to be essential for this purpose: 1) no increase in blood flow on perfusion images obtained by the arterial spin labeling (ASL) method; 2) less microbleeding on T2*-weighted images (T2*). However, we experienced some exceptional cases. Purpose: To clarify the histopathological features of PCNSLs those had atypical radiological findings. Method: 62 consecutive PCNSL cases (40 males, 22 females, mean age 65.4 years, range 35–84) treated in our department from April 2013 to March 2020 were retrospectively analyzed. We compared the following features between 47 biopsy cases showing typical image findings as PCNSLs (Group A) and 15 surgically resected cases with atypical findings (Group B), 1) number of blood vessels per hyper 10 fields, 2) occupying area of blood vessels per unit area, 3) immunoreactivity of vascular endothelial growth factor (VEGF), and 4) germinal center B-cell (GCB) subtype. Results: In Group A, the number of blood vessels in the tumor was 39.3 on average, and the area occupied by blood vessels was 3.8%. In Group B, the former was 133.2, and the latter was 9.9%. There was no significant difference in VEGF expression and GCB subtype. Conclusion: In PCNSLs showing with high blood flow and microbleeds, the blood vessels were rich and partial bleeding was confirmed histologically. We should analyze much more cases to set the threshold both of the ADC value and the absolute value of blood flow calculated by the ASL method to distinguish between PCNSLs and GBs.

INNV-07. THE ROLE OF BIOPSY IN MOLECULAR DIAGNOSIS OF DIFFUSE INTRINSIC PONTINE GLIOMA PATIENTS

Abstract INTRODUCTION Diffuse intrinsic pontine glioma (DIPG) is an aggressive and fatal pediatric brain tumor. Due to its difficult anatomic location and infiltrative nature, DIPGs are not surgically resectable and more than 90% of children die within two years of diagnosis. Historically, standard of care has consisted of clinical and radiological diagnosis followed by palliative radiation for symptomatic relief. Although tumor biopsy is not necessary for diagnosis, there is debate as to whether the procedure provides benefits that outweighs its risk. Recent studies have proposed that biopsy-driven molecular characterization of these tumors can inform prognosis and identify potential treatment targets that could lead to clinical breakthroughs. METHODS This study was a retrospective chart review of 26 patients treated for a DIPG diagnosis between July 1998 and July 2019 at Cohen Children’s Medical Center. We compared outcomes of biopsied vs. non-biopsied DIPG patients through quantitative data analyzing the number and types of treatment given. We analyzed post-surgical data regarding safety of DIPG biopsies which were performed by optical stereotactic needle biopsy or robot-assisted stereotactic biopsy procedures. RESULTS There were no permanent biopsy complications in any patient and biopsy did not delay treatment as average hospital stay was 1.5 days. All biopsies collected sufficient material for next generation sequencing analysis and revealed targetable mutations for available clinical trial therapies. 67% of patients were subsequently enrolled in clinical trials, 75% of which required biopsy results for enrollment. MGMT promoter methylation assay results in all tested DIPG biopsy cases indicated resistance to temozolomide, the most common treatment agent given to non-biopsied patients. CONCLUSION Biopsy of DIPG tumors is a safe and accurate procedure that does not delay treatment and identifies molecular targets for individualized therapy. The role of biopsy in DIPG patients allows for molecular characterization of DIPG tumors which informs and increases treatment options.