68Ga-FAPI PET/CT as an Alternative to 18F-FDG PET/CT in the Imaging of Invasive Lobular Breast Carcinoma.

Accurate staging of invasive lobular carcinoma (ILC), a subtype of breast cancer, is vital for effective clinical management. Although 18F-FDG PET/CT is a commonly used tool, its efficacy varies across different histologic subtypes. To mitigate this challenge, our investigation delves into the potential utility of 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT as an alternative for staging ILC, aiming to address a significant research gap using a more expansive patient cohort than the smaller samples commonly found in the existing literature. Methods: In this retrospective analysis, women diagnosed with primary ILC of the breast underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/CT. Both modalities were compared across all lesion locations with the used reference standard. The interval between scans was 1 wk, without any intervening treatments. Lesions were categorized visually, and tracer activity was analyzed using SUVmax, tumor-to-background uptake ratio, and uptake ratios. Both modalities were compared across various parameters, and statistical analysis was performed using SPSS 22.0. A P value of less than 0.05 was chosen to determine statistical significance. Results: The study included 23 female ILC patients (mean age, 51 y) with hormone-positive, human epidermal growth factor receptor type 2-negative tumors. Most (65%) had the luminal A subtype. 68Ga-FAPI PET/CT outperformed 18F-FDG PET/CT, with higher tumoral activity and tumor-to-background uptake ratios (P < 0.001). Primary tumors showed significantly increased uptake with 68Ga-FAPI PET/CT (P < 0.001), detecting additional foci, including multicentric cancer. Axillary lymph node metastases were more frequent and had higher uptake values with 68Ga-FAPI PET/CT (P = 0.012). Moreover, 68Ga-FAPI PET/CT identified more lesions, including bone and liver metastases. Pathologic features did not significantly correlate with imaging modalities, but a positive correlation was observed between peritumoral lymphocyte ratio and 68Ga-FAPI PET/CT-to-18F-FDG PET/CT uptake ratios (P = 0.026). Conclusion: This study underscores 68Ga-FAPI PET/CT's superiority over 18F-FDG PET/CT for ILC. 68Ga-FAPI PET/CT excels in detecting primary breast masses, axillary lymph nodes, and distant metastases; can complement 18F-FDG PET/CT in ILC; and holds potential as an alternative imaging method in future studies.

A novel predictive model of lymphovascular space invasion in early-stage endometrial cancer.

Objective: To predict lymphovascular space invasion (LVSI) positivity in early-stage (stage 1-2) endometrial cancer (EC) using a predictive model with prognostic factors of EC. Materials and Methods: We included 461 patients who underwent total hysterectomy and bilateral salpingo-oophorectomy with pelvic-paraaortic lymphadenectomy as the primary treatment for presumed early-stage EC at our clinic between 2010 and 2020. Moreover, all surgical specimens were examined histopathologically for the positivity or negativity of LVSI, and the patients were divided into two groups based on these pathologic outcomes. Age, menopausal status, histological type (type 1-2), histological grade (grades 1-2-3), depth of myometrial invasion, and peritoneal cytology results were recorded and analyzed as clinicopathological and demographic characteristics of the patients. The Loess algorithm determined the relationship between the observed and predicted outcomes. The distinction between the algorithms was evaluated by calculating the C-index. Results: LVSI positivity was significantly associated with advanced age, menopause, type 2 EC, advanced histological grade, malignant peritoneal cytology, cervical involvement, and a tumor exceeding 50% of the myometrial depth (p<0.001, respectively). Remarkably, LVSI was most strongly associated with three explanatory variables: 1- More than 50% myometrial invasion [odds ratio (OR): 3.78; 95% confidence interval (CI): 1.80-7.60], 2- Advanced histological grade [OR=1.98 (1.20-3.20) 95% CI], 3- Malignant peritoneal cytology [OR= 3.06 (1.40-6.30) 95% CI]. The penalized maximum likelihood estimation model correctly classified 87% of the included patients (C-index: 0.876). Conclusion: Our predictive model may help predict LVSI based on different prognostic factors. The prognostic factors included in the nomogram were significantly associated with LVSI, particularly myometrial invasion depth of more than 50%, advanced histological grade, and malignant peritoneal cytology.

A case of hepatosplenic sarcoidosis accompanied by hypercalcemia.

We present a case diagnosed with hepatosplenic sarcoidosis with hypercalcemia. Elevated liver enzymes and hypercalcemia were detected in the patient who was admitted to the hospital with abdominal pain and dyspnea. Abdominal dynamic magnetic resonance imaging (MRI) showed diffuse, multiple, nodular hyperintense lesions on T2 weighted. Multinuclear giant cells and lymphocytic portal inflammation were seen in the patient's liver biopsy, whose angiotensin-converting enzyme level was high, and hepatosplenic sarcoidosis was diagnosed. Shortness of breath, abdominal pain, and calcium level improved with methylprednisolone treatment.

Diagnostic accuracy of Thinprep® in cervical lymph node aspiration: Assessment according to the Sydney system.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is a reliable technique that has been used for many years in lymphadenopathy diagnosis. Although conventional smear is the standard approach in FNAC, liquid-based cytology (LBC) is accepted as an alternative method. Reporting standardization is a significant gap in fine-needle aspiration cytology, leading to failure in pathologist-clinician dialog and interobserver variability. In 2020, an expert panel proposed the Sydney system for classifying and reporting lymph node aspiration cytology. This study aimed to evaluate the diagnostic accuracy of LBC in lymph node aspiration cytology under the guidance of the Sydney system. METHODS: Five hundred-four LBC samples were reevaluated and classified according to the Sydney system. Of these, n = 24 were categorized as L1-inadequate/non-diagnostic, n = 283 as L2-benign, n = 36 as L3- atypical cells of undetermined significance/atypical lymphoid cells of uncertain significance (AUS/ALUS), n = 48 as L4-suspicious, and n = 113 as L5-malignant. Four hundred-one samples were histopathologically confirmed. The diagnostic accuracy of LBC and the risk of malignancy for each Sydney category were calculated. RESULTS: The results were as follows: sensitivity 98.97%; specificity 98.60%; positive predictive value 94.80%; negative predictive value 99.29%; and overall diagnostic accuracy 98.75%. The ROM was 16.6% for L1, 0.7% for L2, 88.8% for L3, and 100% for L4 and L5. CONCLUSION: LBC is suitable for use in lymph node aspiration under the guidance of the Sydney system and has high diagnostic accuracy. Future comprehensive studies will increase the applicability of the Sydney system and minimize interobserver variability.

Superiority of 68Ga-FAPI PET/CT scan in detecting additional lesions compared to 18FDG PET/CT scan in breast cancer.

PURPOSE: We compared the ability of 68Ga-FAPI PET//CT with 18FDG PET/CT imaging techniques to detect additional lesions in breast cancer patients that may affect further chemotherapy options. METHODS: A total of 48 patients with breast cancer underwent concurrent 68Ga-FAPI-04 and 18FDG PET/CT regardless of whether they had received chemotherapy or not in the last month before imaging. Both modalities were compared according to various parameters: clinical/pathological features, number of lesions detected, activity uptake (SUVmax), and the effect on the evaluation of response to treatment in the post-chemotherapy group. RESULTS: This retrospective study included 48 patients with breast cancer (mean age 53.3 ± 11.7 years; IDC 89.6%; ILC 10.4%). In the comparison of both modalities, no statistical significance was obtained in terms of the pathological characteristics of the patients. More lesions were demonstrated in all categorized regions in 68Ga-FAPI PET/CT imaging with higher uptake values compared to 18FDG PET/CT in this study. In the treatment response evaluation of the post-chemotherapy group, 12 cases (12/24) who were evaluated as PMR, CMR, or SD according to 18FDG PET/CT results were later accepted as PD due to newly detected lesions in complementary 68Ga-FAPI PET/CT imaging and treatment of patients was managed accordingly by clinicians. CONCLUSION: It was determined that 68Ga-FAPI PET/CT was superior to 18FDG PET/CT in terms of accuracy and it was thought that 68Ga-FAPI PET/CT could be utilized as an additional complementary imaging to 18FDG PET/CT. Moreover, 68Ga-FAPI PET/CT, with its significant theranostic potential, could become a key element in predicting the pathological response of breast cancer patients in further researches.

Molecular characteristics of colorectal hyperplastic polyp subgroups.

BACKGROUND/AIMS: The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. RESULTS: 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. CONCLUSION: Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.

Techniques for Maximizing the Performance of Molecular Pathology Testing: Responsibilities of All Pathologists.

Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities. This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs) and cell-free circulating nucleic acids), effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned. Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.

Analysis of histopathological aspects and bone destruction characteristics in acquired middle ear cholesteatoma of pediatric and adult patients.

OBJECTIVE: The aim of this study was to investigate the proliferative and apoptotic activity of middle ear cholesteatoma in pediatric and adult patients, in addition to comparing its histopathological aspects and the severity of advanced bone destruction. MATERIALS AND METHODS: Medical records of 223 patients treated for chronic otitis media with cholesteatoma at the Otolaryngology Department of Dokuz Eylul University between January 1992 and December 2013 were retrospectively evaluated. Sixty-one patients subjected to tympanomastoidectomy due to middle ear cholesteatoma, with sufficient specimens for histopathological examination, were included in the study. Sections of archived tissues in paraffin blocks were subjected to new histopathological examinations. The proliferative and apoptotic activities of cholesteatoma were determined by immunohistochemical staining for epithelial thickness (ET), and Ki-67 and caspase-3 expression. A novel scoring system, the Bone Erosion Score (BES), was developed to estimate the severity of bone destruction. The Austin-Kartush classification score (AKCS) was also calculated. RESULTS: ET and Ki-67 expression was higher in adult patients than in the pediatric patients (p=0.009 and 0.01, respectively); however, caspase-3 immunopositivity did not show any significant intergroup differences (p=0.106). The differences in AKCS and BES between pediatric and adult patients were not statistically significant. According to the correlation analysis, a significant positive correlation was observed between AKCS and BES (p=0.001), and between ET and Ki-67 expression (when histopathological data were compared) (p=0.001). CONCLUSION: The proliferative activity of cholesteatoma was higher in adult patients. Therefore, these findings do not support the theory that the aggressive clinical course of cholesteatoma in pediatric patients is correlated with its histopathological characteristics.

Undifferentiated Laryngeal Carcinoma with Pagetoid Spread.

Pagetoid spread, is used to define intraepithelial spread of cancer cells, when a massive carcinoma is identified beneath the basal membrane. There are only few reports of pagetoid spread at the head and neck region. Herein a 74 year old male patient with bilateral transglottic laryngeal high grade malignant epithelial tumor with pagetoid spread is presented. The tumor was located at the submucosa and there was spread of the CK7 and CK19 positive tumor cells into the non neoplastic mucosa, which was CK5/6 positive, sparing the basement membrane, creating a typical pagetoid pattern. Radiographic and positron emission tomography scan examination of the patient was unremarkable at presentation other than the laryngeal and neck lesions; but extensive systemic metastasis developed at 6 months following operation. To the best of our knowledge no epithelial malignancy with pagetoid spread was described at the larynx. Pagetoid spread may be a hallmark of very aggressive behavior in laryngeal carcinoma.

Assessment of Subepithelial Angiogenesis in Acquired Cholesteatoma between Pediatric and Adult Patients.

OBJECTIVE: The aim of this study was to compare subepithelial angiogenesis developing within the perimatrix of the cholesteatoma between pediatric and adult patients. METHODS: Sixty-one patients who underwent mastoidectomy for the first intent because of chronic otitis media with cholesteatoma between 1993 and 2013 and from whom appropriate tissue specimens were taken were included in the study. The patients were classified in the pediatric patient group if they were under the age of 18 years and the adult patient group if they were 18 years and older. Immunohistochemical staining for CD-31 was performed on new sections taken during surgery and sections prepared from archived tissues in paraffin blocks. Results were compared between the groups. RESULTS: A total of 61 patients, of whom 25 were pediatric and 36 were adult patients, were included in the study. The mean CD-31 immunopositive microvessel rates were 8.8 (3-15) and 6.61 (2-14) for the pediatric and adult patient groups, respectively. The difference between the groups was statistically significant (p=0.037). Correlation analysis showed a statistically significant negative correlation between the CD-31 immunopositive microvessel rates and age (p=0.036). CONCLUSION: Subepithelial angiogenesis developing within the perimatrix of the cholesteatoma of the pediatric patients was more expressed than that of the adult patients.