Atypical meningiomas are diagnosed in the presence of: (1) three or more of the following minor atypical criteria: increased cellularity, small cells with a high nuclear/cytoplasmic ratio, prominent ...nucleoli, sheeting, and foci of spontaneous or geographic necrosis; (2) mitotic count ≥ 4 mitoses per 10 HPF (high mitotic index); (3) brain invasion. The 5-year disease-free survival (DFS) is around 50%. Due to their heterogeneous behavior, the post-surgical treatment of atypical meningiomas is controversial. This study investigated the ability of histopathological features to predict recurrence risk of atypical meningiomas. Meningiomas classified as atypical only on minor atypical criteria had low recurrence risk. Brain invasion, high mitotic index and sheeting were significantly associated with shorter disease-free survival (DFS) (
P
= 0.001;
P
= 0.01;
P
= 0.01). The presence of brain invasion and the co-presence of sheeting and high mitotic index had the highest ability to identify recurring meningiomas (
P
= 0.0001) (sensitivity: 90.9%; specificity: 86.7%). Our results suggest reconsideration of classification of meningiomas as atypical based only on minor atypical criteria. The presence of brain invasion and the co-occurrence of sheeting and high mitotic count may be useful to identify high risk cases, which may benefit from adjuvant treatments.
AIM To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and ...surgery.METHODS Tumor regression grade(TRG) according to the Dworak system and yT NM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced(c TNM stage Ⅱ and Ⅲ) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival(DFS) and cancer specific survival(CSS) was analyzed by Kaplan Meier and Cox-regression analyses.RESULTS cN + status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response(low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified twotiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The twotiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables. CONCLUSION Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with c N+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.
Due to their widely variable clinical behavior, the post‐surgical treatment of atypical meningiomas is controversial. Therefore, prognostic factors able to identify high‐risk cases, which may benefit ...from adjuvant treatments, are warranted. Mammalian target of rapamycin (mTOR) belongs to the PI3K‐AKT pathway. Its phosphorylated form (p‐mTOR Ser2448) is involved in cell growth, differentiation and tumorigenesis. The aim of this study was to evaluate p‐mTOR Ser2448 expression and its eventual correlation with clinicopathological features, recurrence, or disease‐free survival (DFS), in atypical meningiomas. p‐mTOR immunohistochemical expression was analyzed in 48 atypical meningiomas and correlated with clinicopathological parameters and with DFS. Eighty‐one percent of atypical meningiomas expressed p‐mTOR Ser2448. High immuno‐expression was significantly associated with recurrences (P = 0.01) and lower DFS (P = 0.01). The presence of brain invasion, high mitotic index plus sheeting, and Simpson grade were significant and independent prognostic variables at multivariate analysis. p‐mTOR Ser2448 is expressed in atypical meningiomas. High expression predicts development of recurrences and shorter DFS in patients affected by these tumors. Since p‐mTOR Ser2448 is a target of anti‐neoplastic drugs, evaluation of its expression may be used, not only to identify atypical meningiomas at higher risk of recurrence, but also to select those to submit to adjuvant targeted chemotherapy.
Atypical teratoid rhabdoid tumor (ATRT) is an aggressive tumor of the CNS and characteristically occurs in the pediatric age. In adulthood, ATRT is rare and it is mainly localized in the cerebral ...hemispheres. Only 16 cases of ATRT have been described in the sellar region up to now. Interestingly, all sellar ATRTs occurred in adult female patients. Herein we report a novel case of sellar ATRT in a patient with previous history of lactotroph adenoma. Similar to other sellar ATRTs, this case occurred in a female adult patient. At histological examination, it was characterized by a small number of rhabdoid cells. In addition, it did not have homozygous deletion of SMARCB1 gene, but it rather showed a frameshift mutation at exon 4 of SMARCB1 which had not been previously found in ATRT. Clinico‐pathological and molecular findings observed in this case confirm previous evidence that sellar ATRT seems to be a distinct entity. Association with previous prolactin‐secreting pituitary adenoma is discussed.
We report a unique case of dual-genotype oligoastrocytoma characterized by IDH2 gene mutation. The tumor was resected from the temporal lobe of a 25-year-old man. At histological examination with ...hematoxylin and eosin stain, it showed distinct oligodendroglial and astrocytic areas. The former retained alpha-thalassaemia/mental retardation X-linked (ATRX) immuno-expression and had absent staining for p53, while the latter had ATRX loss and p53 over-expression. Molecular analyses were separately assessed in the 2 tumor components. Gene sequencing disclosed IDH2 mutation in both, whereas oligodendroglial, but not astrocytic areas, had 1p/19q codeletion and telomerase reverse transcriptase promoter mutation. Distinction of dual-genotype oligoastrocytoma from oligodendroglioma and astrocytoma might be clinically relevant for prognosis and therapy. Because most studies that investigated the molecular phenotype of oligoastrocytomas have focused on IDH1 R132H mutated cases, we suggest further analyses on diffuse gliomas with heterogeneous (astrocytic and oligodendroglial) morphology before oligoastrocytoma is dismissed as a distinct nosological entity.
Aims
The clinical outcome of patients with locally advanced rectal cancer who undergo neoadjuvant chemoradiotherapy (CRT) is influenced by the tumour response to treatment, which is reflected by ...tumour regression grade and post‐treatment (y) TNM stage. Little is known about the prognostic value of pretreatment histopathological features of the tumour that may be useful to discriminate potential non‐responders and to design tailored therapeutic strategies. In this study, we aimed to investigate the prognostic role of poorly differentiated clusters (PDCs) of neoplastic cells in pretreatment biopsies of patients with rectal cancer treated with neoadjuvant CRT.
Methods and results
Grading based on PDC counting was retrospectively applied to 204 pretreatment endoscopic biopsies of rectal carcinomas from patients treated with neoadjuvant CRT and surgery. Interobserver agreement in the assessment of PDC grade was good. High PDC grade was significantly associated with high yT stage (P = 0.044), yM+ status (P = 0.0004), and unchanged TNM stage or TNM upstaging (P = 0.032). In addition, high PDC grade was a significant and independent prognostic factor for cancer‐specific survival.
Conclusions
PDC grade may be assessed in preoperative biopsies of rectal cancer with good reproducibility. High PDC grade in a pretreatment tumour is significantly associated with a poor response to therapy. Hence, we suggest that PDC grading might be used as a significant predictive and prognostic factor in patients with locally advanced rectal cancer who are treated with neoadjuvant CRT, and to identify high‐risk patients who need surgery and adjuvant chemotherapy.
The prognosis of patients with colorectal liver metastases (LMs) is mostly established on clinical variables or on the anatomic extent of colorectal cancer (CRC). Histopathological factors of LMs ...which may actually reflect the biological aggressiveness of the tumor are not routinely considered to define the risk of worse clinical outcome in those patients. The number of poorly differentiated clusters (PDCs) of neoplastic cells in primary CRC is associated with metastatic risk and bad prognosis, but PDC presence in LMs has been barely analyzed thus far. We assessed PDC presence in the histological slides of surgically resected and synchronous LMs in 63 patients with CRC who had been not submitted to any neoadjuvant treatments. Then, we analyzed its association with patients’ cancer-specific survival (CSS) or progression-free survival. The presence of PDCs (P = .016) and PDC localization at tumor edge of LMs (P = .0004) were significantly associated with shorter CSS. PDC presence at the periphery of LMs and positive resection margin were independent prognostic variables for CSS. PDC localization at the tumor edge of LMs was a significant (P = .0079) and independent prognosticator of shorter progression-free survival. Our data suggest that PDC presence and peripheral localization in LMs may be relevant to predict outcome and useful for clinical decision making in patients with colorectal synchronous LMs.
•The prognosis of patients with colorectal LM is commonly established on clinical features.•Low attention is given to histopathological features of LM as prognostic factors.•The number of PDCs in primary CRC is correlated with prognosis and metastatic disease.•This study shows that PDC presence and peripheral localization in synchronous colorectal LMs are associated with bad prognosis.•Assessment of PDC counting in synchronous LMs may be useful to assess prognosis and for clinical decision making in patients with stage IV CRC.