Diffuse hemispheric glioma with H3 p.K28M (K27M) mutation: Unusual non-midline presentation of diffuse midline glioma, H3 K27M-altered?

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called "diffuse hemispheric glioma with H3 p.K28M (K27M) mutation" (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in both cases. Overall, DHG-H3 K27 is an unusual group of diffuse gliomas that shows similar clinical, histopathological, genomic, and epigenetic features to DMG-H3 K27 as well as enrichment for activating alterations in MAPK pathway genes. These findings suggest that DHG-H3 K27 is closely related to DMG-H3 K27 and may represent an unusual presentation of DMG-H3 K27 without apparent midline involvement and with frequent MAPK pathway activation. Detailed reports of additional cases with clinical follow-up will be important to expand our understanding of this unusual group of diffuse gliomas and to better define the clinical outcome and how to classify DHG-H3 K27.

Two cases of pineal anlage tumor with molecular analysis.

Pineal anlage tumor is a rare pediatric tumor with clinical and histological features overlapping with pineoblastoma. Two patients with pineal anlage tumor, a 13-month-old female and an 11-month-old male, underwent subtotal resection, high-dose chemotherapy with autologous stem cell rescue, and radiation. Neither had tumor progression 50 months after diagnosis. The tumors underwent next-generation sequencing on a panel of 340 genes. Chromosomal copy gains and losses were present and differed between the tumors. No mutations or amplifications, including none specific to pineoblastoma, were identified.

Occult primary breast cancer presenting with brachial plexopathy: A case report.

Breast cancer affects about one in eight women over the course of her lifetime. Occult breast cancer, in which primary breast cancer is detected without evidence of disease in the breast itself, comprises up to 1% of new diagnoses; this is typically detected from abnormal axillary lymph nodes, and distant metastases are rare. Here, we present an unusual case of occult breast cancer presenting as upper extremity pain, edema, and weakness, with a metastatic mass to the brachial plexus being the only site of disease.

Metastatic Renal Cell Carcinoma Masquerading as a Sphenoid Wing Meningioma.

A 47-year-old man who presented with subacute binocular diplopia and a left head turn was found to have a right sixth nerve palsy and right optic disc edema. Radiologic imaging revealed a non-lytic right greater sphenoid wing mass with a dural tail, suggestive of a sphenoid wing meningioma. The patient underwent an orbitotomy with lesion biopsy; histopathologic analysis and subsequent imaging revealed the diagnosis of metastatic clear cell renal cell carcinoma. He developed new metastases despite systemic immunotherapy, and prognosis was guarded at last follow up 3 months after diagnosis. The authors present the first reported case of renal cell carcinoma metastatic to the sphenoid wing without sinus involvement, describing an atypical presentation of an aggressive malignancy that necessitates timely diagnosis for possible survival.

Histological features and prognostic significance of treatment effect in lymph node metastasis in head and neck squamous cell carcinoma.

AIMS AND OBJECTIVES: Cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) is common. Pre-operative chemoradiotherapy (preCRT) and postoperative chemoradiotherapy (postCRT) is frequently employed in such patients. The prognostic value of viable SCC, treatment effect or no SCC in resected lymph nodes in patients who received or did not receive preCRT and postCRT was investigated. METHODS AND RESULTS: Resected cervical lymph nodes from 146 patients with HNSCC were evaluated for viable SCC, treatment effect or no SCC. Immunostains for Ki67, cyclin D1, caspase 3 and H2AFX were performed on viable SCC or nucleate keratin debris. Clinical and histological data were correlated with tumour recurrence or persistence. Patients with nucleate keratin debris in lymph nodes had outcomes similar to those with diffuse treatment effect and no SCC. Viable tumour in lymph nodes was associated with worse prognosis in patients who received preCRT (P = 0.01). This relative worsening of prognosis was not observed in patients with oropharyngeal SCC or recurrent disease. Lower proliferation index in lymph node SCC was associated with preCRT and with worse outcomes (P = 0.0002). Overall, patients who received preCRT or postCRT had outcomes not significantly different from those who did not. CONCLUSION: The presence of viable SCC in cervical lymph nodes has prognostic import when taken in context with the patient's history. Viable SCC in lymph nodes was significantly associated with worse outcome among patients with non-oropharyngeal SCC who received preCRT. Nucleate keratin debris should not be considered viable SCC in lymph nodes.

Rapidly Growing Pancreatic Adenocarcinoma Presenting as an Irreducible Umbilical Hernia.

Hernia sacs are a common anatomic pathology specimen, which rarely contain malignancy. We present a case of rapidly growing pancreatic adenocarcinoma, which initially presented as metastasis to an umbilical hernia sac. The patient was a 55-year-old male with a two-year history of umbilical hernia. Two months prior to herniorrhaphy, the hernia became painful and the patient experienced nausea and weight loss. The gross examination did not reveal distinct lesions. Microscopically, the hernia sac was diffusely infiltrated by moderately differentiated adenocarcinoma, which was positive for CK7 and pancytokeratin and negative for TTF-1, CK20, PSA, and CDX2. Clinical laboratory tests found elevated levels of CA 19-9 and CEA. Computed tomography scan with intravenous contrast showed a 5 cm ill-defined and hypoattenuating mass involving the pancreatic tail and body, as well as numerous ill-defined lesions in the liver and peritoneal carcinomatosis. The patient had an earlier noncontrast computed tomography scan four months prior to the surgery, which did not detect any lesions in the abdomen. This case highlights the importance of intravenous contrast with computed tomography for the evaluation of pancreatic lesions and also emphasizes the importance of thorough histologic evaluation of hernia sacs for the detection of occult malignancy.

Molecular basis of substrate recognition and degradation by human presequence protease.

Human presequence protease (hPreP) is an M16 metalloprotease localized in mitochondria. There, hPreP facilitates proteostasis by utilizing an ∼13,300-Å(3) catalytic chamber to degrade a diverse array of potentially toxic peptides, including mitochondrial presequences and ß-amyloid (Aß), the latter of which contributes to Alzheimer disease pathogenesis. Here, we report crystal structures for hPreP alone and in complex with Aß, which show that hPreP uses size exclusion and charge complementation for substrate recognition. These structures also reveal hPreP-specific features that permit a diverse array of peptides, with distinct distributions of charged and hydrophobic residues, to be specifically captured, cleaved, and have their amyloidogenic features destroyed. SAXS analysis demonstrates that hPreP in solution exists in dynamic equilibrium between closed and open states, with the former being preferred. Furthermore, Aß binding induces the closed state and hPreP dimerization. Together, these data reveal the molecular basis for flexible yet specific substrate recognition and degradation by hPreP.