The histopathologic report of surgically resected colorectal liver metastases: What is clinically relevant?

Colorectal carcinoma (CRC) is one of the most common malignancies and a major cause of cancer-related death worldwide. The liver is the most frequent site of metastatic spread, so that about half of the patients with CRC have or develop liver metastases (LM) during the clinical course of the disease. Colorectal LM can potentially be cured by surgery, but most patients still experience disease progression and recurrence after the surgical treatment. Prediction of a patient's post-surgical clinical course is mainly based on clinical parameters or the histopathological features of the primary tumor, while little attention is given to the pathological characteristics of the LM. In this paper, we review the prognostic relevance of the gross and microscopic pathological features observed in surgically resected LM and propose which information should be included in the histopathological report to guide surgeons and oncologists for the subsequent therapeutic management

Recurrent primary endobronchial fetal rhabdomyoma: a case report and literature review

Fetal rhabdomyoma is an extremely rare benign rhabdomyoblastic tumor with myotube-like differentiation, mainly arising on mucosal surfaces of the head and neck region of both children and young patients, almost invariably definitively treated with surgical excision. Herein the case of a male adult suffering from a recurrent fetal rhabdomyoma primary involving the bronchial structures is reported, along with a detailed literature review. This is the first fetal rhabdomyoma described to originate in such a localization; furthermore, an 11-year interval period between the first lesion and the recurrent one has never been reported

Glioblastoma with tumor-to-tumor metastasis from lung adenocarcinoma

Glioblastoma is a tumor with widely variable morphology. It may rarely show pseudoepithelial components or true epithelial differentiation. Metastasis to glioblastomas have been previously reported, but were unsupported by immunohistochemical or molecular analyses. Herein we describe a glioblastoma with carcinomatous foci in a patient with no past clinical history of tumors outside the central nervous system. The carcinomatous foci expressed epithelial, but not glial markers. Therefore, whole-body imaging was carried out to verify the presence of carcinoma. A lung mass was biopsied and it resulted as primary lung adenocarcinoma. Carcinomatous foci of glioblastoma and lung adenocarcinoma had the same KRAS mutation which was absent in glial areas of the glioblastoma. Thus, glioblastoma with tumor-to-tumor metastasis was diagnosed. This case demonstrates that, albeit rare, metastases to glioblastoma may occur, and they should be considered in the differential diagnosis of glioblastoma with carcinomatous foci. Even when the past clinical history is negative, the presence of carcinoma should be investigated to rule out glioblastoma with tumor-to-tumor metastasis

Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival

The use of adjuvant therapy is controversial in atypical meningiomas with gross total resection. Predictors of recurrence risk could be useful in selecting patients for additional treatments. The aim of this study was to investigate whether molecular features are associated with recurrence risk of atypical meningiomas. According to WHO classification, the diagnosis of atypical meningioma was based on the presence of one major criteria (mitotic activity, brain invasion) or three or more minor criteria. The molecular profile of 22 cases (eight mitotically active, eight brain-invasive, and six with minor criteria) was assessed exploring the mutational status and copy number variation of 409 genes using next generation sequencing. Of the 22 patients with a median follow up of 53.5 months, 13 had recurrence of disease within 68 months. NF2 mutation was the only recurrent alteration (11/22) and was unrelated to clinical-pathological features. Recurring meningiomas featured a significantly higher proportion of copy number losses than non-recurring ones (p = 0.027). Chromosome 18q heterozygous loss or CDKN2A/B homozygous deletion was significantly associated with shorter recurrence-free survival (p = 0.008; hazard ratio: 5.3). Atypical meningiomas could be tested routinely for these genetic alterations to identify cases for adjuvant treatment

A risk score based on 5 clinico-pathological variables predicts recurrence of atypical meningiomas

The use of adjuvant radiotherapy is controversial in patients with atypical meningiomas treated with gross total resection (GTR). This study aimed to determine whether clinico-pathological features could be helpful to predict the recurrence risk in this group of patients and to identify high-risk ones who could benefit from adjuvant treatment. We collected 200 patients with primary atypical meningiomas treated with GTR but with no adjuvant radiotherapy from 5 different centers. A risk score, formulated by assigning 1 point for the presence and 0 points for the absence of 5 high-risk parameters (male sex, parasagittal site, Simpson grade 3, mitotic index\u2009 65\u20096/10 HPF, and sheeting), was the most significant predictor of recurrence. A score 652 was associated with 4.7 risk of shorter disease-free survival (p\u2009<\u20090.0001). Our findings indicate that the presence of at least 2 clinico-pathological high-risk factors predicts recurrence of totally resected primary atypical meningiomas and could be helpful for identifying patients who could benefit from adjuvant radiotherapy

Next-generation repeat-free FISH probes for DNA amplification in glioblastoma in vivo: Improving patient selection to MDM2-targeted inhibitors

A next-generation FISH probe mapping to the MDM2 locus-specific region has recently been designed. The level of MDM2 gene amplification (high versus low) may allow selection of patients for cancer treatment with MDM2 inhibitors and may predict their responsiveness. We investigated the spectrum of MDM2 gene alterations using the new probes in vivo after visualizing single neoplastic cells in situ from a series of glioblastomas. Signals from next-generation repeat-free FISH interphase probes were identified in tissue microarrays that included 3 spots for each of the 48 cases. The murine double minutes (MDM2)-specific DNA probe and the satellite enumeration probe for chromosome 12 were used. Three cases (6%) showed more than 25 signals (high gene amplification), and 7 (15%) showed 3-10 signals (gains); among these, 4 cases (8%) had an equal number of MDM2 and centromeric signals on chromosome 12 (polyploidy). Genomic heterogeneity was observed only in 3 cases with low gene amplification. In our series, 6% of glioblastomas exhibited high MDM2 amplification (in vivo) with a pattern related to the known double minutes/chromothripsis phenomenon (in situ), and only cases with low amplification showed genomic heterogeneity. We concluded that the rate of MDM2 gene amplification can be a useful predictive biomarker to improve patient selection