Citations

ABSTRACT Objective Pituitary carcinoma (PC) is defined by the presence of metastasis from a pituitary tumour. PC is rare, therefore information regarding survival and factors influencing survival are limited. We sought to assess overall survival following the diagnosis of PC and to determine factors associated with outcome. Design Retrospective case series. Patients Patients with PC who attended the Mayo clinic between 1997 and 2025. Measurements Information regarding patient demographics, tumour characteristics, management and outcomes were extracted. Results In total 25 patients (11 women, 44%) were diagnosed with PC (median age 56 years, range, 44–78). The most common cell type was a corticotroph tumour ( n = 15, 60%). All but one patient had pituitary directed surgery and all received pituitary adenoma (PA) directed radiation therapy. Metastases were identified a median 6 years (range, 1–32) after initial PA diagnosis. At last follow‐up, 10 (40%) patients were alive, 12 (48%) died of PC, and 3 (12%) died from other causes. The median survival time of patients from PC diagnosis was 3 years. The 1‐, 5‐ and 10‐year survival rates were 59%, 37% and 15%, respectively. Increased survival probability was associated with temozolomide treatment ( n = 9) at some point in treatment plan ( p = 0.026), the use of systemic therapy vs locoregional treatment ( p = 0.045), female sex ( p = 0.011), and in nonfunctional tumours ( p = 0.023). Conclusion PC carries a poor prognosis, with a median survival of only 3 years. Improved survival was associated with temozolomide exposure, female sex, and nonfunctional tumour subtype and underscores the prognostic relevance of tumour biology and treatment approach.

Purpose: To describe a case of locally invasive conjunctival squamous cell carcinoma (SCC) refractory to plaque radiotherapy. Case Description: A 69-year-old man presented with a recurrent conjunctival tumor after 6 previous cycles of topical 5-fluorouracil chemotherapy and excisional biopsy showing invasive SCC with positive margins. There was a mild anterior chamber reaction. By the time of repeat excisional biopsy, the conjunctiva had ulcerated with underlying scleralysis associated with histopathologic evidence of scleral involvement by SCC. After subsequent tectonic scleral patch grafting, plaque radiotherapy was applied after which the disease appeared to be controlled for 9 months. The eye then developed progressive conjunctival ulceration and scleralysis with progressive ectropion. Exenteration was performed, revealing locally invasive SCC into palpebral conjunctiva, ciliary body, and choroid. Conclusions: Conjunctival SCC can be locally invasive with destruction of the globe, despite plaque radiotherapy. Clinicians should be suspicious of invasive diseases in cases of ocular surface squamous neoplasia that are poorly responsive to topical chemotherapy. Associated anterior chamber cell and progressive scleralysis should also raise concern for invasive malignancy.

Abstract Diffuse hemispheric glioma, H3 G34‐mutant (DHG‐H3 G34) has been primarily molecularly characterized by methylation profiling and sequencing studies. We describe an integrated histomolecular evaluation including high‐resolution copy number profiling of a series of 60 DHG‐H3 G34 to further our understanding of the spectrum of genetic changes associated with this tumor type. Cases were clinically tested using an 187‐gene mutation and fusion targeted neuro‐oncology next‐generation sequencing panel ( n = 60) and Oncoscan chromosomal microarray ( n = 26) by a single laboratory (2018–2022). A subset of cases had immunohistochemical results for OLIG2 ( n = 42), p53 ( n = 48), and ATRX ( n = 46), and methylation array data ( n = 8). Median age at testing was 21 years (range, 12–50). No significant difference was noted in clinical, histopathological, and mutational profile between pediatric and adult patients. H3‐3A G34 mutations included G34R ( n = 56; 94%), G34V ( n = 3), and a non‐canonical G34E ( n = 1). Concurrent mutations most often involved TP53 ( n = 55; 92%), ATRX ( n = 50; 83%), and PDGFRA ( n = 34; 57%). A reportedly primary tumor was confirmed to be hypermutant and had a PMS2 mutation. A single case also showed an FGFR3::FAM184B fusion. All cases with available chromosomal microarray data had unbalanced genomes, which were often complex (14/26; 54%). The most frequent recurrent copy number abnormalities were losses involving 3q, 4q, 10q, 13q, and 18q, and 17p copy‐neutral loss of heterozygosity (cnLOH) encompassing TP53 . This copy number profile was reminiscent of that seen in Grade 4 IDH‐mutant astrocytomas. Collectively, a TP53 abnormality at copy number (12/26, all cnLOH), sequence (55/60) and protein expression (46/48) level was detected in all 60 cases. In conclusion, integrated high‐resolution copy number and histomolecular analysis expanded the spectrum of genetic changes associated with DHG‐H3 G34, including the presence of universal TP53 abnormalities with frequent cnLOH—a copy number abnormality that has been largely unrecognized—for this new 2021 World Health Organization central nervous system tumor type.

Abstract In adult-type diffuse gliomas CDKN2A and/or CDKN2B (CDKN2A/B) deletions often co-occur with deletion of MTAP, suggesting that MTAP immunohistochemistry (IHC) may be a surrogate marker of CDKN2A/B status. However, the association between CDKN2A/B and MTAP deletion at the genomic level remains unknown. We assessed CDKN2A/B and MTAP deletions by chromosomal microarray in 333 adult-type diffuse gliomas and performed MTAP IHC on a subset (n = 63). CDKN2A/B and MTAP deletions were detected in 216 and 215 cases, respectively, and were concurrent in 99.5% (215/216). While most tumors with CDKN2A/B homozygous deletion (n = 148) showed concurrent MTAP homozygous deletion (108/148; 73.0%), a subset harbored MTAP heterozygous deletion (39/148; 26.4%). By analyzing the size of the chromosomal alterations, we demonstrate that initial large chromosomal 9p losses result in concurrent heterozygous deletion of CDKN2A/B and MTAP whereas smaller “second hit” deletions leading to homozygous CDKN2A/B deletion do not always encompass the MTAP locus. Discordant CDKN2A/B and MTAP tumors affect the association between MTAP IHC and copy number status of MTAP and CDKN2A/B. These findings suggest that adult-type diffuse gliomas, regardless of IDH status, follow a stereotypic pathway involving concurrent CDKN2A/B and MTAP heterozygous deletion but may diverge for CDKN2A/B and MTAP homozygous deletion.

Abstract MGMT is primarily inactivated via promoter methylation, but MGMT homozygous deletion (hmzdel) has been rarely reported as an alternative inactivating mechanism. Although functionally similar to a methylated MGMT promoter, MGMT hmzdel is associated with an unmethylated MGMT promoter test result reflecting the MGMT promoter status of the non-neoplastic cells invariably present in any tumor specimen. Thus, patients whose tumors have MGMT hmzdel (and unmethylated MGMT promoter) would be inaccurately predicted to lack benefit from alkylating chemotherapy based on MGMT promoter methylation testing alone. To evaluate the impact of this clinical scenario, we estimated the frequency and distribution of MGMT hmzdel in routine clinical testing of CNS tumors. Among 12,424 CNS tumors (3,044 with provided diagnosis of glioblastoma) tested using Oncoscan chromosomal microarray (2015-2025), 10 tumors (0.08%) had MGMT hmzdel: 8 with entire gene hmzdel and 2 with partial gene hmzdel favored to be inactivating (RNA-sequencing underway to exclude possibility of activating rearrangements). All tumors were supratentorial and non-midline. Median age at diagnosis was 58.5 years (range, 34-81), with 3:2 male:female. Of the 10 cases, 9 (of 3,044; 0.3%) had integrated diagnosis of glioblastoma, IDH-wildtype; the remaining case was a recurrent astrocytoma, IDH-mutant, CNS WHO grade 4. All 10 cases had loss of chromosome 10q and a highly unmethylated MGMT promoter by droplet digital PCR testing of downstream CpG sites 75-80/84-87, with median fraction abundance of 0.19% (range, 0-0.85). In summary, MGMT hmzdel only occurred in high-grade adult-type diffuse astrocytic gliomas, and is a rare potential pitfall for MGMT promoter methylation testing leading to inaccurate patient stratification. It is critical that laboratories performing routine CNS tumor copy number testing include MGMT in the curated list of reportable genes, and that clinicians be aware of this rare clinical scenario to accurately stratify patients despite misleading MGMT promoter test results.

Purpose: To present a case of a dislocated posterior lamellar graft into the vitreous cavity in an eye that was post pars plana vitrectomy. Methods: Retrospective case report Results: A middle-aged man underwent pars plana vitrectomy (PPV), pars plana lensectomy (PPL), and SSIOL fixation following a traumatic eye injury. The patient required subsequent Descemet stripping automated endothelial keratoplasty (DSAEK) for corneal edema, and the posterior lamellar graft was lost intraoperatively into the posterior segment. The graft was surgically retrieved one week later, followed by a successful placement of a new posterior lamellar graft. Histopathological examination of the retrieved graft after one week in the vitreous cavity revealed viable endothelial cells, a novel finding in a posteriorly dislocated DSAEK graft. The newly placed graft remained attached and healed well, with the patient achieving a visual acuity (VA) of 20/80 at three months post-operatively. Discussion: Posteriorly dislocated grafts may be suitable for transplantation to the corneal stroma following prompt retrieval from the vitreous cavity. Prompt retrieval and appropriate surgical techniques are critical for optimizing outcomes in such clinical scenarios.

Abstract BACKGROUND Adamantinomatous craniopharyngiomas (ACPs) are rare, partially cystic central nervous system tumors driven by the WNT/β-catenin pathway. As they grow, ACPs compress the surrounding pituitary gland, optic chiasm, and third ventricle. ACPs are highly morbid tumors with enormous quality of life impact on patients, often early in life. Thus, better treatments are needed. Current ACP treatment consists of maximally safe surgical resection with radiation for residual disease. Complete surgical resection is challenging, and recurrence is common. Targeted systemic chemotherapy is not routinely used for ACP treatment. Interleukin-6 (IL-6) levels are elevated within ACPs compared to normal brain tissue, making IL-6 an intriguing therapeutic target. Treatment response of ACP to tocilizumab alone or in combination with bevacizumab has been reported in children. MATERIAL AND METHODS We retrospectively reviewed the medical records of three adults with recurrent ACP who received combination treatment with bevacizumab and tocilizumab on a compassionate basis between June 2022 and April 2025 at Mayo Clinic in Rochester, MN. We collected demographic, clinical, treatment, radiologic, and outcome data. RESULTS All three patients were male and median age at initial ACP diagnosis was 38 years (range: 32-42 years). All patients underwent subtotal resection followed by radiation therapy. One patient had repeat surgical resection and two patients required interventions for hydrocephalus. At the time of ACP recurrence, all patients had visual impairment, endocrine dysfunction, and headaches. All patients received bevacizumab (7.5 mg/kg q3 weeks) and tocilizumab (8 mg/kg q3 weeks [n=2] or 4 mg/kg q4 weeks [n=1]). While receiving combination therapy, ACP tumor volume decreased on magnetic resonance imaging for all three patients (64%, 68%, and 29% reduction). None exhibited tumor growth since starting combination therapy. One patient had a small intraparenchymal hemorrhage, suspected secondary to radiation-induced cavernous malformation, so bevacizumab was discontinued, and he remains on tocilizumab alone. The other two patients continue combination therapy (for 344 and 351 days). Two patients experienced improvement in vision, and one had improvement in cognition. Possible adverse effects of treatment included sinus infections, fatigue, neutropenia, and hypertension. CONCLUSION Treatment with combination bevacizumab and tocilizumab was associated with shrinkage of ACP tumors and clinical improvements and obviated the need for further surgery or radiation in all three patients. This combination of medications may reprogram the tumor microenvironment, leading to ACP involution. This well-tolerated regimen provides a noninvasive option for treatment of recurrent ACP, and potentially initial ACP treatment, and may improve quality of life for patients.