ACT-5 Prognosis of IDH-mut lower-grade gliomas in Hokkaido University Hospital

Background: WHO grade 2 and 3 adult gliomas are nowadays getting together as lower-grade gliomas (LrGGs), but we had been recognized grade 3 (G3) tumors as high-grade and grade 2 (G2) tumors as low-grade. In this report, we investigate the treatment and prognosis of the patients with LrGG harboring IDH mutations in our institutions. Methods:We retrospectively review primary treatments and their prognosis for LrGG patients with IDH mutation since 2003. They categorized as astrocytomas and oligodendrogliomas according to 1p/19q loss-of-heterozygosity status. Prognosis were evaluated by overall survival. Postoperative primary treatments applied chemo-radiotherapy (CRT), radiotherapy only (RT), chemotherapy only (CT), and observation (Ob). Results: 36 astrocytomas and 60 oligodendrogliomas were identified. In astrocytomas, the patients with G3 (N=16) were treated by CRT (N=14) or CT (N=2), and the patients with G2 (N=20) were treated by CRT (N=2), RT (N=3), CT (N=3), or Ob (N=12). In oligodendrogliomas, the patients with G3 (N=34) were treated by CRT (N=32) or CT (N=2), and the patients with G2 (N=26) were treated by CRT (N=3), RT (N=1), CT (N=5), or Ob (N=17). 10-year survival rate (10yOS) of astrocytomas and oligodendrogliomas are 54% and 90%, respectively (p=0.002). According to histological malignancy, 10yOS of G3 and G2 astrocytomas were 54% and 54%, respectively (p=0.97) and that of G3 and G2 oligodendrogliomas were 86% and 100%, respectively (p=0.64). In both group, there are no different of prognosis according to histological malignancy. Discussion: There was no prognostic different between G2 and G3 astrocytomas in our institution. Since the treatment intensity for G2 and G3 astrocytomas were clearly different, the primary treatment for G2 astrocytomas might be insufficient. On the other hand, there were no prognostic different between G2 and G3 oligodendrogliomas in our institution, as with recent reports, so the primary treatment intensity for oligodendrogliomas should be appropriate.

Ki-67 and mitotic index in triple-positive breast cancer.

e12551 Background: A grade in breast cancer is the strongest prognostic factor. In the new edition of the AJCC 8th, the tumor grade is one of the criteria that determines patients with breast cancer in the prognostic groups. According to the Nottingham system the mitotic count (MC) mostly determines the grade. Interobserver reproducibility for MC is not as good as for IHC marker phh3. The group of triple-positive breast cancer (TPBC) is characterized by the presence of a crosstalk mechanism between the signaling pathways of ER and HER2, which leads to the development of resistance to therapy. However, according to the 8th AJCC, patients with ER+/HER2+ belong to a more favorable prognostic group. Methods: We selected 284 patients with early BC who received treatment at our centre from 2012 to 2020 and didn’t receive presurgical therapy. The patients were divided according to the surrogate subtype into triple-positive (n = 90) and other subtypes (n = 194). The Ki-67, the number of nuclei of tumor cells stained with anti-phh3 antibody, the cell density of the tumor per 1 mm2 and the number of phh3 + per 1000 tumor cells were assessed. Results: Visually accessed number of mitoses was grade 3 in 30% of tumors in the TPBC group and 29% in the second group. There was no statistically significant difference in the Ki-67 index of proliferative activity in the two studied groups. In the TPBC group the median Ki-67 was 16.8%, in the second group - 18.3% (p = 0.376516), while the groups differed significantly in terms of the phh3 index (the median in the TPBC was 23.7/mm2, the median in the second group - 16.06/mm2, p = 0.024703). The groups also significantly differed in the number of nuclei of tumor cells that directly entered the mitotic phase (5.1/1000 nuclei in the TPBC group versus 3.2/1000 nuclei in the second group, p = 0.003901). Conclusions: Despite similar indices of proliferative activity in the TPBC and non-TPBC groups, mitotic activity and the number of directly dividing tumor cells in the TPBC group are significantly higher than in the rest of the BC population. Considering the criteria for assessing phh3 (MC 1 < 4/mm2, MC 2 2 4 to 7/mm2, MC 3 > 7/mm2), most TPBCs will have a histological malignancy grade of 3, which according to AJCC 8th places them in the group of poor outcome. We suggest that these differences may be due to the crosstalk mechanism. The second conclusion of our study is the fact that Ki-67 is a poor predictor of the MC.

Role of Twist and Podoplanin in Partial Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

The aim of this study was to perform a comparative analysis of podoplanin (PDPN) and Twist immunoexpressions in lower lip and oral tongue squamous cell carcinomas (LLSCC and OTSCC, respectively). PDPN and Twist immunoexpressions were semi-quantitatively evaluated by analyzing the invasion front, the compressive areas, the large islands and nests and dissociated cells of the chosen carcinomas. Their statistical associations and correlations with clinical-pathological characteristics were verified by the Mann-Whitney and Spearman’s test. Twist expression was low in both carcinomas, with <25% labeling on the invasive front. Significant differences were observed for LLSCC (p=0.032) and OTSCC (p=0.025) regarding PDPN immunoexpression in relation to the worst invasion patterns determined by a histological malignancy gradation system. Statistically significant negative correlations between PDPN membrane expression and general (r=-0.356, p=0.024) and cytoplasmic Twist expressions (r=-0.336; p=0.034) in LLSCC were also observed. Twist and PDPN are suggested to be associated to a more aggressive invasion pattern in both LLSCC and OTSCC cases but not related to the different biological behaviors on these anatomical sites. Also, it was seen that PDPN membrane expression is inversely related to general and cytoplasmic Twist expression in LLSCC cases.

Form-Vessel Classification of Cholangioscopy Findings to Diagnose Biliary Tract Carcinoma’s Superficial Spread

We aimed to evaluate a newly developed peroral cholangioscopy (POCS) classification system by comparing classified lesions with histological and genetic findings. We analyzed 30 biopsied specimens from 11 patients with biliary tract cancer (BTC) who underwent POCS. An original classification of POCS findings was made based on the biliary surface’s form (F factor, 4 grades) and vessel structure (V-factor, 3 grades). Findings were then compared with those of corresponding biopsy specimens analyzed histologically and by next-generation sequencing to identify somatic mutations. In addition, the histology of postoperative surgical stumps and preoperative POCS findings were compared. Histological malignancy rate in biopsied specimens increased with increasing F- and V-factor scores (F1, 0%; F1, 25%; F3, 50%; F4, 62.5%; p = 0.0015; V1, 0%; V2, 20%; V3, 70%; p < 0.001). Furthermore, we observed a statistically significant increase of the mutant allele frequency of mutated genes with increasing F- and V-factor scores (F factor, p = 0.0050; V-factor, p < 0.001). All surgical stumps were accurately diagnosed using POCS findings. The F–V classification of POCS findings is both histologically and genetically valid and will contribute to the methods of diagnosing the superficial spread of BTC tumors.

Spindle cell sarcomas, suggestive of peripheral nerve sheath tumours, arising in the tongues of two cats

Case summary Two domestic shorthair cats, one an 11-year-old female neutered cat and the other a 13-year-old male neutered cat, presented with partly raised, well-demarcated masses at the rostral tip of the tongue. Histological examination and immunohistochemical staining were consistent with sarcomas, and were most suggestive of peripheral nerve sheath tumours. One tumour had histological features consistent with a malignant peripheral nerve sheath tumour (PNST). Relevance and novel information Feline PNSTs arising on the tongue are rarely described in the published literature, and, to our knowledge, a case of malignant PNST originating at this site has not been described to date. Therefore, this represents a new differential diagnosis for cats presenting with a lingual mass. Regardless of histological malignancy, in cats these tumours have the potential for local recurrence but appear very unlikely to metastasise.

Symptoms of colorectal cancer contributes to its localization and advancement

<b>Introduction:</b> Colorectal cancer is one of the most common cancers occurring in Poland. Unfortunately, this cancer is most often diagnosed at the time of great advancement. This is caused by the appearance of specific symptoms only in the late stages of cancer. Also, such low detection of early stages of adenocarcinoma may be caused by disregarding of slight symptoms. <br/>Purpose:</b> To analyse symptoms in patients with colorectal cancer and correlate with chosen clinical-pathological parameters. <br/>Materials and methods:</b> The study group consisted of 46 patients diagnosed with colorectal cancer. Information on symptoms associated with cancer (subjective and objective) have been selected from patients' medical history. The presence of these symptoms was correlated with the age and sex of patients, tumor location, histological type of cancer, grade of histological malignancy (G), stage of tumor (T stage), presence of lymph node metastases and distant metastases. <br/><b>Results:</b> It has been shown that the presence of pain complaints described by the patient are associated with the occurrence of cancer in the colon. The painfulness and pathological resistance diagnosed by the physician are more often associated with cancer located in the colon. In the case of tumors located in the rectum, faecal admixtures appear more frequently. It has also been shown that the presence of admixtures of blood and mucus in the stool is associated with more advanced local tumors, infiltrating pericolorectal tissues (T3 + T4). <br/><b>Conclusions:</b> Familiarity with clinical symptoms of colorectal cancer could make patients more sensitive to more often screening for cancer. Analysis of these symptoms could indicate to the physician the location or stage of the cancer.

Neuroendocrine tumors: An epidemiological study of 250 cases at a tertiary hospital

Summary Objective: To compare the frequency of neuroendocrine tumors in our service with that reported in the literature considering age, gender, location, degree of differentiation and increase in incidence by means of a retrospective study. Method: Search of variables from a database of neuroendocrine tumor cases diagnosed at the Department of Pathological Sciences, Hospital da Santa Casa de São Paulo over the past 10 years, relating them to epidemiological data such as gender, age, distribution across organs, most-used immunohistochemical markers and presence or absence of either lymph node or distant metastases. Results: In all, 250 cases were reviewed, 133 involving females, predominantly in the 61-70 age range. The lung was the most frequent site, followed by the stomach. CD56, synaptophysin and chromogranin were the immunohistochemical markers used most often and to a lesser extent Ki67, a marker of cell proliferation that indicates a higher or lower degree of histological malignancy. Metastases, either in lymph nodes and/or distant sites, were found in 44 cases (17.6%). Conclusion: The results were largely consistent with those in the literature, including age group, gender and location. Most metastases originated from high-grade tumors, with high Ki67 levels and greater impairment of the liver. However, only 36.4% of the cases had Ki67 index. Reevaluation of the Ki67 proliferative index using image analysis in doubtful cases will allow for a correlation between progression and prognosis.

Epidemiological Study of Canine Mast Cell Tumours According to the Histological Malignancy Grade

The aim of the study was to identify significant relationships between the tumour malignancy grade and dogs’ age, breed, sex, size, and location of mast cell tumours (MCTs). MCTs accounted for 13.27% of all diagnosed canine skin tumours. The highest incidence was recorded among Boxers, Labrador Retrievers, American Staffordshire Terriers, and Golden Retrievers. Statistical analysis revealed significantly higher probability of occurrence of the grade I mast cell tumour in the French Bulldog in the head, neck, torso, and limb regions, the grade-II mast cell tumour in Boxer, Doberman, Dachshund, shepherds, and setters in the scrotal region, and the grade III mast cell tumour in Shar-Pei in the axilla region. In the group of the oldest dogs aged 11-16, there was higher risk of development of MCTs grade II and III. Young dogs (aged 2-3 and 4-6) were found to be more prone to development of MCTs grade I. There was no correlation between MCTs grade and dogs’ sex and size. To the authors’ knowledge this is the first report on statistical relationships between the degree of mast cell tumour malignancy and dogs’ phenotypic traits, age and tumour location. This analysis indicate predilections for development of the particular mast cell tumour malignancy degrees in certain dog breeds, age, and anatomical location

Atypical aspirates of the breast: a dilemma in current cytology practice

AimsThe probabilistic approach is widely adopted for breast fine needle aspiration cytology. However, a definite cytological diagnosis is not always possible for C3 (atypia) cases, which poses a management dilemma as this represents a mixed category of benign and malignant cases. It would be beneficial to be able to predict malignancy based on specific cytological features in C3 aspirates.MethodsA comprehensive panel of cytological features (including quantitative, cytomorphological and background features) in a large cohort of C3 breast aspirates with subsequent histological excisions was evaluated to identify relevant morphological criteria predicting the risk of subsequent malignancy.ResultsA total of 229 C3 specimens with histological follow-up were included. Malignant outcome was found in 30.1% of specimens and the majority were invasive cancers. Features that showed a significant association with malignant outcome included older age (p=0.001), lower percentage of epithelial cell clusters and high percentage of single cells (p=0.002), cribriform architecture in cell clusters (p=0.034), presence of intracellular mucin (p=0.027), increased cell clusters without myoepithelial cells (p=0.048), diminished fibromyxoid stromal fragments (p=0.001), reduced bipolar nuclei (p=0.021) and the presence of necrosis (p=0.023). Except for the percentages of single cells and cell clusters without myoepithelial cells, all other features were shown to be independent risk predictors in multivariate analysis.ConclusionsC3 aspirates were associated with a significant probability of histological malignancy. Certain quantitative, cytomorphological and background features were potentially helpful in predicting the risk of a malignant outcome. The prediction could be clinically useful in the management of C3 cases.