Molecular analysis with pancreaseq® in evaluation and management of pancreatic cysts: A cohort of 28 patients.

Objectives: Herein, we present the PancreaSeq® results of 28 patients and emphasize the usefulness of molecular testing in evaluation of pancreatic cysts. Material and Methods: A total of 10 (35.7%) non-diagnostic, 6 (21.4%) negative, 5 (17.8%) atypical, and 7 (25%) were positive for mucinous cystic neoplasm (MCN) pancreatic cyst aspirates were analyzed with PancreaSeq® at Mayo Clinic, Jacksonville between September 2021 and February 2023. Results: Three non-diagnostic, two negative, three atypical, and two positive for MCN cysts were positive for KRAS and GNAS mutations. They were interpreted as intraductal papillary mucinous neoplasm (IPMN) with low risk for progression to high-grade dysplasia/adenocarcinoma. One negative case was positive for KRAS and GNAS mutation and RNF43 copy number alteration. It was interpreted as IPMN with a low risk of progression. Two non-diagnostic, one negative, and two positive for MCN cysts were positive for KRAS mutation. All were interpreted as IPMN/MCNs with low risk of progression. One positive for MCN case was positive for GNAS mutation and ALK fusion and one positive for MCN case was positive for GNAS mutation, ALK fusion, and RNF43 copy number alteration. Both were interpreted as IPMN and their risk of progression was interpreted as not well understood. One atypical case was positive for KRAS and TP53 mutation and was interpreted as IPMN/ MCNs with a high risk of progression. VHL mutation was present in one non-diagnostic case. It was interpreted as serous cystadenoma and the risk for progression was low. Conclusion: Molecular analysis of pancreatic cysts with PancreaSeq® is useful in accurate diagnosis, especially when cytologic material is non-diagnostic and helps improve patient management.

Evaluating Low HER2 Status in Invasive Breast Carcinoma via HER2 Immunohistochemistry, with HER2 FISH Correlation: A Cohort of 112 Patients.

Introduction: Recent trials demonstrated clinically significant benefits in HER2-nonamplified breast cancer with HER2-low expression using novel anti-HER2 antibody-drug conjugates. Thus, HER2-low breast cancer was proposed as a separate diagnostic entity. Herein, we reclassify HER2-negative cancers according to the new HER2-low category using a modified system and further investigate HER2-very-low expression. Methods: 114 HER2 immunohistochemistry (IHC)-negative invasive breast tumors were identified from the pathology database of Mayo Clinic, Jacksonville, FL, between January 2019 and August 2022. Two blinded breast pathologists (BP) independently rescored HER2 IHC slides at 200x and 400x magnification. Discordant cases between the two BPs were rescored together. The most recent 2018 ASCO/CAP HER2 scoring criteria were used. HER2 (0) was subdivided into HER2 (absent) and HER2 (very low). HER2 FISH testing was performed in all cases. Results: The cohort comprised of 38 (33.3%) HER2 (0) and 76 (66.7%) HER2 (1+) tumors. The first round of rescoring at 200x and 400x magnification resulted in 17 (14.9%) HER2 (absent), 31 (27.2%) HER2 (very low), and 64 (56.2%) HER2 (1+) and 2 (1.8%) HER2 (2+) tumors by BP1 and 20 (17.5%) HER2 (absent), 33 (28.9%) HER2 (very low), and 61 (53.5%) HER2 (1+) tumors by BP2. The combined final rescoring by BP1 and BP2 was as follows: 15 (13.2%) HER2 (absent), 35 (30.7%) HER2 (very low), 63 (55.3%) HER2 (1+), and 1 (0.9%) HER2 (2+) cases. A comparison of the first round of rescoring between two BPs showed substantial agreement with Cohen's kappa value of 0.67. Both comparisons of first rescoring by BP1 and by BP2 to combined final rescoring showed almost perfect agreement with Cohen's kappa value of 0.83.Follow-up FISH studies showed one amplified tumor. Conclusion: Our data support the need for finer granularity, classification, and understanding of HER2-low breast cancers. We also show that reproducibility between trained BP can be obtained, albeit with scoring at high power and low threshold for showing challenging interpretations.

Two unique cases of metastatic malignant melanoma of the gastrointestinal tract.

INTRODUCTION AND IMPORTANCE: Gastrointestinal tract (GIT) is a common site for malignant melanoma metastasis, with small bowel being the most common. It is usually difficult to diagnose at an early stage because of the anatomical location of the disease. It is also challenging for pathologists to diagnose due to the small amount of biopsy samples. Survival rates of melanoma patients with distant metastasis are very poor. CASE PRESENTATION: This study presents two males, aged 67 and 69 years old, who have metastatic melanoma within the GIT. One was metastasis to the esophagus and another with metastasis to the jejunum presenting as intraluminal masses. Their clinical history and pathologic features of the metastasis are evaluated to give an insight into this disease. CLINICAL DISCUSSION: Gastrointestinal melanoma is hard to detect due to its anatomical location and limited ability to biopsy. Typically, they present at an advanced stage when diagnosed. Approximately 60 % of patients with cutaneous melanoma will have GIT metastasis at the time of autopsy. The small bowel was found to have an affinity for malignant melanoma due to the expression of the CCR9 ligand, CCL25. BRAF mutations are much less observed in GIT mucosal melanomas as compared to cutaneous melanomas. Furthermore, AKAP13-NTRK3 fusion has been reported specifically in the GIT mucosal melanomas. NTRK fusions in general can be observed in metastatic melanomas and have been reported in GIT metastatic melanomas. CONCLUSION: GIT malignant melanomas are difficult to detect due to their anatomical location, with poor prognosis, and have a unique genetic profile.

Metastatic Thyroid Carcinoma to the Kidneys Presenting Initially as Bilateral Renal Masses: A Rare Case Report and Literature Review.

Thyroid cancers exist in multiple forms. Papillary and follicular carcinomas of the thyroid are often referred to as well-differentiated thyroid cancers. Well-differentiated thyroid cancers rarely present as a distant metastatic cancer on initial diagnosis. Papillary thyroid cancer tends to have a good prognosis; however, if distant metastasis of PTC is present, there is usually a poor clinical outcome with a less favorable prognosis. In this study, we report a 90-year-old female who presented with right-sided abdominal discomfort. A renal ultrasound revealed bilateral upper pole renal masses. A percutaneous biopsy was ordered, and the microscopic examination revealed bilateral renal metastasis with a follicular variant of papillary thyroid carcinoma. The patient underwent thyroidectomy and sustained radiation therapy for her bilateral renal metastases. She died 6 years after her initial diagnosis, due to sepsis. This is the second study in literature to report bilateral renal metastasis of follicular variant of papillary thyroid cancer.

Management of pediatric cerebral cavernous malformations with gamma knife radiosurgery: a report of 46 cases.

INTRODUCTION: Pediatric cerebral cavernous malformations (CCMs) are commonly treated vascular anomalies with different clinical characteristics than their adult counterparts. Outcomes of Gamma Knife Radiosurgery (GKRS) for pediatric CCMs have not explicitly been reported. This paper reports our experience in managing pediatric CCMs with GKRS. METHODS: We retrospectively reviewed the clinical features, GKRS parameters, and clinical and radiological outcomes of 46 children with 64 CCMs. RESULTS: A total of 46 children, including 19 girls and 27 boys, with a median age of 16 years (3-17 years), were enrolled in the study. The median age at first CCM diagnosis was 13 years (range, 2-17 years). Twenty-two patients (47.8%) had more than one neurological symptom at the time of diagnosis, and the most common presenting symptom was seizure (28.3%). The most common location was supratentorial superficial (53.1%), and 17.4% of patients had multiple CCMs. A developmental venous anomaly was detected in 5 patients (10.9%). During a total of 52.4 retrospective patient-years in patients with > 1 hemorrhage episode, the calculated annual hemorrhage rate was 40.1%. The median post-GKRS follow-up was 79 months (range, 19-175 months), with an overall 306.2 prospective patient years. The annual hemorrhage rate (AHR) during the first 2 years after GKRS and after the initial 2 years was 1.11% and 0.46%, respectively. Regarding clinical factors and GKRS parameters, univariate analysis revealed a significant association with post-GKRS AHR and volume (p = 0.023) only. Patients with pre-GKRS seizures showed favorable seizure control (Engel class I and II) in 8 children (61.5%). There was no mortality in our series. CONCLUSION: Low AHR following GKRS with no radiation-induced toxicity makes GKRS a therapeutic alternative for pediatric CCMs.

Gamma Knife radiosurgery for tuberculum sellae meningiomas: a series of 78 consecutive patients.

Outcomes of Gamma Knife radiosurgery (GKRS) for tuberculum sellae meningiomas (TSMs) have not been reported explicitly within any meningioma series. We present the first and largest TSM series with clinical, radiosurgical, and outcome features for 78 consecutive patients managed with GKRS. Patients who underwent GKRS for TSMs between 2005 and 2021 and had a minimum of 6 months of follow-up were included. Medical records, imaging studies, and follow-up examinations were evaluated retrospectively. A total of 78 patients with a median age of 50.5 years were included. SRS was conducted as an upfront treatment for 38 patients (48.7%). The median target volume was 1.7 cm3 (range, 0.1-14.6). During a median follow-up of 78.5 months, the cumulative PFS rates of the whole cohort at 1, 5, and 10 years by Kaplan-Meier analysis were 100%, 97.9%, and 94.5%, respectively. Of 47 patients with impaired vision, improvement and/or preservation of visual acuity, and visual field were achieved in 55.3% and 42.6%, respectively. No new-onset hormonal deficits were observed. Based on our data, SRS represents an effective and safe modality for unresected or recurrent/residual TSMs. SRS should be offered to patients who are not willing or not ideal candidates for surgery.