Glioblastoma multiforme with oculomotor nerve involvement: case report and literature review.

Gliomas involving the cranial nerves III-XIII are rare. Even rarer are glioblastomas multiforme (GBMs) with only 10 cases previously reported. Oculomotor nerve involvement was described in only 2 patients. The mechanisms proposed so far include an origin from the nerve itself or an extension within the nerve of a midbrain tumor. We report the case of a 69-year-old man who presented with an isolated left oculomotor nerve palsy. He was found to have a left temporal GBM extended to the frontal lobe. Diagnostics and intraoperative and pathological findings clearly demonstrated a massive infiltration of the cisternal portion of the left oculomotor nerve. We suppose this could be the first case of direct oculomotor nerve invasion by exophytic spread of a supratentorial GBM or by subarachnoid seeding from a temporal tumor. Less probably, it could be the first case of an oculomotor nerve GBM with a temporal lobe invasion.

Intramedullary spinal cord metastasis from an adenoid cystic carcinoma of the external auditory canal: case report.

BACKGROUND AND IMPORTANCE: Intramedullary spinal cord metastases (ISCMs) are rare and no cases of ISCM from an adenoid cystic carcinoma (ACC) of the external auditory canal (EAC) have been reported. CLINICAL PRESENTATION: We report a 54-year old man complaining backpain and worsening myelopathy. He had an ACC of the EAC resected years prior. A spinal MRI demonstrated a contrast-enhancing intramedullary lesion within the conus medullaris. The histopathological diagnosis of the patient was consistent with the patient's primary cancer. At 3 months follow-up, the neurological condition of the patient was unchanged. CONCLUSIONS: This is the first reported case of ISCM from a primary ACC of the EAC.

Resected atypical meningioma relapsed to anaplastic meningioma during luteinizing hormone-releasing hormone agonist therapy.

A 55-year old man with a history of meningioma treated with LHRH-agonist plus radiotherapy for prostate cancer (PCa) experienced a meningioma growth during hormone therapy (HT). Meningioma was radically resected revealing an atypical meningioma and HT was continued due to the high risk of PCa relapse until symptomatic meningioma relapse occurred after further 10 months. Gross lesions were radically removed and histology revealed anaplastic meningioma. This is the first case of rapid meningioma evolution to an anaplastic histology during LHRH-agonist.

Oil Red O Is a Useful Tool to Assess Donor Liver Steatosis on Frozen Sections During Transplantation.

Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation. Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory. The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies. METHODS: Twenty consecutive liver biopsies of donors were collected during transplantation procedures from September 2017 to February 2018 at the Institute of Pathology of the University and Hospital Trust of Verona, Italy. Each liver biopsy was cut at a different thickness (3, 5, and 8 µm) and stained with both Oil Red O and conventional hematoxylin and eosin for intraoperative consultation. The degree (percentage of hepatocytes involved) of fatty changes was recorded. The results obtained during the intraoperative consultation were finally compared with the formalin-fixed and paraffin-embedded permanent section. RESULTS: Assessment of steatosis on hematoxylin and eosin frozen sections was reported as mild in 17 cases (85%), moderate in 2 cases (10%) and severe in 1 case (5%). Oil Red O frozen sections reported the following results: mild steatosis in 16 cases (80%), moderate in 2 cases (10%), and severe in 2 cases (10%). The percentage of liver steatosis obtained with Oil Red O was consistent in all cases with that of the permanent sections. The staining procedure for Oil Red O required approximately 18 minutes. CONCLUSIONS: Oil Red O special stain is a fast and inexpensive tool to improve the assessment of steatosis on frozen biopsies during liver transplantation.

Fast Chromotrope Aniline Blue Special Stain Is a Useful Tool to Assess Fibrosis on Liver Biopsy During Transplantation.

BACKGROUND: Assessment of potential liver allograft donors with frozen sections has clinical relevant consequences for the transplant recipient. Several clinical risk factors have been identified that increase the risk of transplantation failure and it is critical for the pathologist to become familiar with the histologic criteria for donor liver suitability. In this setting an accurate and reliable assessment of fibrosis is crucial. We sought to report the value of the rapid chromotrope aniline blue stain (CAB) in a transplantation clinical work-flow for scoring liver fibrosis. MATERIALS AND METHODS: Twenty consecutive intraoperative donor liver biopsy specimens were evaluated by a pathologist at the Transplant Pathology Board Room, AOUI Verona, during 24-hour on-call service. The stage of fibrosis was evaluated according to Ishak score ranging from 0 to 6 (absent to cirrhosis) using hematoxylin and eosin stain (H&E) plus rapid CAB special stain. After a 3-week washout period, only the slides stained with H&E were re-assessed for fibrosis stage by the same pathologist blinded to donor patient data. RESULTS: Combination H&E-CAB staging fibrosis score was higher in 20%, lower in 10%, and the same in 70% of biopsy specimens as determined using only H&E stain alone. Rapid CAB stain takes 20 minutes longer than H&E stain alone. CONCLUSIONS: CAB staining may be performed on frozen tissue from liver biopsy during a transplantation process without a significant delay in diagnosis. Combination H&E-CAB staining improves sensibility of interpretation of fibrosis.

Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Ependymoma with diffuse signet-ring features: report of a case and review of the literature.

Signet-ring cell ependymoma is a rare variant of ependymoma with only seven cases described in literature. Biological behavior and prognosis of this entity are not well-known until now. We present a case of a 49-year-old female with a history of headache and gait instability. Magnetic resonance imaging showed an upper cervical tumor with cystic component and mural nodule. The patient underwent surgery. Microscopically some cells displayed an eccentric nucleus compressed to the periphery by vacuolated cytoplasm. Perivascular pseudorosettes and ependymal rosettes were seen only focally. The cells were positive for glial fibrillary acidic protein and epithelial membrane antigen. The diagnosis was ependymoma with diffuse signet-ring features, grade II according to the World Health Organization. It may be difficult to diagnose this unusual variant of ependymoma especially on small biopsies or frozen sections. A complete examination of the specimen is recommended with immunohistochemical confirmation to rule out potential morphologic mimics, such as metastatic adenocarcinomas and gliomas in the differential diagnosis.

SEM, TEM, and IHC Analysis of the Sinus Node and Its Implications for the Cardiac Conduction System.

More than 100 years after the discovery of the sinus node (SN) by Keith and Flack, the function and structure of the SN have not been completely established yet. The anatomic architecture of the SN has often been described as devoid of an organized structure; the origin of the sinus impulse is still a matter of debate, and a definite description of the long postulated internodal specialized tract conducting the impulse from the SN to the atrioventricular node (AVN) is still missing. In our previously published study, we proposed a morphologically ordered structure for the SN. As a confirmation of what was presented then, we have added the results of additional observations regarding the structural particularities of the SN. We investigated the morphology of the sinus node in the human hearts of healthy individuals using histochemical, immunohistochemical, optical, and electron microscopy (SEM, TEM). Our results confirmed that the SN presents a previously unseen highly organized architecture.

Focal C4d staining in peritubular capillaries and kidney graft survival: results of a retrospective study.

A diffuse positivity (>or=50%) of C4d in kidney graft peritubular capillaries (PTC) significantly correlates with the presence of acute or chronic antibody-mediated rejection. In contrast, significance of a "focal" deposit (10%-50%) is not yet completely defined. The purpose of this study was to assess the impact of focal positive C4d staining on graft survival. We retrospectively reviewed 63 renal biopsies in 54 kidney transplant recipients. They were performed between January 2005 and December 2008 because of graft impairement, namely, a significant increase in serum creatinine and/or urinary protein. C4d positivity was assessed by immunohistochemistry on paraffin-embedded sections, in combination with conventional histopathologic evaluation. Biopsies were classified as negative (<10%) versus with focal (10%-50%) or diffuse deposits (>50%). Cumulative survival was calculated by the Kaplan-Meier method, and Cox regression analysis was used for the multivariate analysis. Focal C4d staining in PTC significantly correlated with worse graft survival (P = .006), similarly to diffuse C4d staining. On multivariate analysis, focal C4d staining prognostically correlated with graft survival, but not recipient or donor age, prior transplantation, number of HLA mismatches or the presence of tubulitis in the sample. Focal C4d staining was associated with worse graft survival.

Is protracted low-dose temozolomide feasible in glioma patients?

The authors investigated the safety of 75 mg/m2 temozolomide for 21 days every 28 days in glioma patients. This schedule could lead to DNA repair enzyme O6-alkylguanine-DNA alkyltransferase depletion, contributing to overcoming drug resistance. Although Phase III studies are forthcoming, no data are available on the long-term toxicity of temozolomide, which, in this series, incurred prolonged, cumulative lymphopenia, which leads to a high incidence of infections.

Prognostic factors in childhood intracranial ependymomas: the role of age and tumor location.

Despite several clinical reports on intracranial ependymomas in children, the factors which affect prognosis, and the possibility that certain combinations of factors might limit survival, are still a matter of debate. Between 1976 and 1996 we operated on 35 children with intracranial ependymomas. Postoperative irradiation was given to 27 patients, with associated chemotherapy in 6 cases. Mean follow-up was 62 months. In 12 patients a 5-year follow-up was possible. In October 1996, 18 patients (51.4%) were still alive, the longest disease-free follow-up being 20 years, and the shortest 8 months. We analyzed the prognostic relevance of eight factors. For each factor, different subgroups were distinguished and compared as follows: age at diagnosis (<4 vs. >/=4 years), sex, tumor location (supratentorial vs. infratentorial), tumor size (<4 vs. 4-7 vs. >7 cm), surgical removal (total vs. subtotal), histology (low-grade vs. anaplastic), morphology (solid vs. cystic), adjuvant therapies (treatment vs. no treatment). Two-way contingency tables were made to identify associations between variables. The only significant association was between age and tumor location (p = 0.022): in children under 4, tumors were almost invariably located in the posterior fossa (9 out of 10 cases) with a clear preference for the lateral recess (8 cases). Other correlations were not significant. Kaplan-Meier survival curves were compared to assess the prognostic relevance of each factor. Survival was significantly lower for children under 4, for those with posterior fossa tumors, and for patients with residual tumor (p < 0.05). A multivariate analysis compared variables which significantly affected survival, revealing that age is the most important factor affecting prognosis (p < 0.05), while tumor location and surgical removal do not add any significance to the effect of age on survival. We conclude that age has the strongest prognostic relevance in childhood intracranial ependymomas, while the effect of tumor location on survival may be related to the high incidence of lateral recess ependymomas in younger children.

Computerized tomography and magnetic resonance guided stereotactic brain biopsy in nonimmunocompromised and AIDS patients.

BACKGROUND: The utility of stereotactic brain biopsy (SBB) in AIDS patients still remains controversial. The authors investigated SBB-related diagnostic accuracy, complications, and postoperative sequelae in nonimmunocompromised (NIC) patients and AIDS patients. The role of bioptic yield in treatment planning was also studied in AIDS patients. METHODS: From 1990-95, 200 computerized tomography (CT) or magnetic resonance imaging (MRI)-guided SBBs were performed in our Department; 172 bioptic procedures were performed in NIC patients (169), and 28 SBBs in AIDS patients (27). The statistical significance was evaluated using the Fisher exact t-test. RESULTS: SBB accuracy was very high in both NIC (94.8%) and AIDS (92.9%) patients. Statistical analysis indicated nonsignificant (NS) differences between the two study groups (P > 0.05). Diagnostic yield resulted higher in contrast-enhancing (CE) brain lesions (98.6% in NIC and 95.0% in AIDS patients; P > 0.05; NS), than in non-CE lesions (74.1% in NIC and 87.5% in AIDS patients; P > 0.05; NS). The overall complication rate was similar in both groups (17.2% in NIC and 14.8% in AIDS patients, P > 0.05, NS). The most frequent complication was hemorrhage, with statistically negligible differences between the two study groups (P > 0.05). The frequency of complications involving minor/major morbidity or mortality was very low in NIC (5.9%, 0.6%, and 2.4%, respectively), and in AIDS (3.7%, 7.4%, and 0.0%, respectively) patients. Regarding the therapeutic impact of bioptic diagnosis for neuro-AIDS patients, the preoperative treatment attitude was modified in 23/27 cases (85.2%), and the empiric anti-toxoplasmosis regimen was changed or withdrawn in 17/21 patients (81.0%). CONCLUSION: Our experience demonstrated SBB to be an accurate, manageable, and reasonably safe diagnostic tool in both NIC and AIDS patients. These results suggest also that timely SBB indication in selected AIDS patients, reaching an early diagnosis, may on one side prevent unnecessary and potentially toxic empiric therapeutic regimens, and on the other address the appropriate treatment, thereby improving length and quality of life in such patients.

Familial cavernous hemangioma with atypical neuroimaging.

Three members of the same family were studied, all of whom had multiple intracerebral cavernous angiomas for which a dominant autosomal inheritance was hypothesised. The proband suffered from headaches, and physical examination revealed evident right hemiparesis. The second case started with a hemorrhagic cerebral stroke and the third was asymptomatic on neurological examination. Nuclear magnetic resonance (NMR), performed in two of the three cases, showed lesions whose number and extent were not radiologically characteristic of cavernous angioma. A cerebral biopsy of the proband enabled the diagnosis to be made. Despite the recent introduction of NMR, the nosological classification of familial forms can be difficult when the radiological lesions are atypical. In such cases, cerebral biopsy is not only a valid diagnostic aid, but is also indispensable for obtaining adequate genetic information.

Benign cystic mesothelioma in a male patient: surgical treatment by the laparoscopic route.

We report a case of a benign cystic mesothelioma in a 44-year-old man. The patient was asymptomatic, and the cystic formation was discovered by chance in the course of ultrasonography for urological disorders. Benign cystic mesothelioma is a rare pathology, and only 19 cases have been described in male patients. The differential diagnosis versus other cystic diseases can only be defined histologically and is of critical importance to clinical management. Surgery is mandatory for both diagnosis and treatment. In the case reported here, a minimally invasive laparoscopic approach allowed not only histological diagnosis of benign cystic mesothelioma, but also its surgical treatment by the same route.

Gamma Knife radiosurgery in AIDS-related primary central nervous system lymphoma.

The frequency of AIDS-associated primary central nervous system (PCNS) lymphoma is rapidly increasing in adults and children. In AIDS-related PCNS lymphoma, different authors have reported an overall poorer response rate to conventional radiation compared with immunocompetent patients. This poorer response consists of a significantly positive, although transient effect on survival following radiotherapy (XRT), with a poor toleration for prolonged whole-brain RT (WBR) and with radiation-induced changes within the normal CNS tissue on autopsy examinations after a course of XRT. These observations led us to consider highly focused single-session radiosurgical treatments as a potentially useful therapeutic modality for AIDS-associated PCNS lymphomas. A multi-institutional diagnostic and therapeutic protocol for the evaluation and treatment of AIDS patients with high-risk intracerebral space-occupying lesions has been developed at the University Hospital of Verona. Therapy is based on tumor biopsy. Tumors < or = 3.5 cm in diameter are subjected to Gamma Knife radiosurgery, whereas tumors < or = 4.5 cm are treated with stereotactic brachytherapy. At the Department of Neurosurgery, Verona, Italy, Gamma Knife treatment was performed in 2 cases of deep-seated histologically verified malignant non-Hodgkin's lymphoma. A short-term cliniconeuroradiological follow-up (2 months later) showed neurologic improvement and virtually complete disappearance of the tumor in both patients. The excellent local control and the well-tolerated single-session treatment and absence of brain toxicity signs on CT scan indicate a putative role for Gamma Knife radiosurgery in the treatment of these patients.

p53 protein in low-grade astrocytomas: a study with long-term follow-up.

The immunohistochemical expression of p53 protein (p53) was examined in 52 patients out of a series of 66 patients with low-grade astrocytomas with long-term follow-up. All patients were also evaluated for several clinical and histological features, among which only preoperative Karnofsky score and the extent of surgery were statistically significant parameters to predict outcome on multivariate analysis. p53 accumulation was seen in 46.1% of patients, with a wide range of percentage of positive cells. Median survival for p53-positive and p53-negative patients was 41 and 37 months respectively. The survival curves of p53-positive and -negative patients were not statistically different. However, the curves showed a trend towards a more aggressive course in p53-positive patients beginning 3-4 years after surgery. Five years after diagnosis the survival estimate with the Kaplan-Meier method was 21.2% for patients with p53-positive tumours and 45.9% for patients with p53-negative tumours. This trend is not due to different distribution of major clinical prognostic factors (age, incomplete resection or Karnofsky status). The trend could be related to the time needed by the p53-positive clone to outgrow the rest of the p53-negative neoplastic cell population. This hypothesis is further supported by the fact that the five recurrences which were surgically removed (one anaplastic astrocytoma and four glioblastomas) derived from p53-positive tumours and were themselves intensely p53 positive.

Morphology of sweat glands in determining time of death.

This study demonstrates post-mortem autolytic alterations in the skin at cellular and subcellular levels and identifies parameters which may assist in determining the time of death in the first few hours post-mortem. Serial skin samples from the ventral surface of the arm were taken at intervals of 3, 6, 9 and 12 h after death in 29 subjects of various ages, with no signs of skin disease; causes of death were various. Three types of tests were performed: cytochemical (hematoxylin-eosin and alcian-PAS), immunohistochemical (S-100, CEA, Cytokeratin, ASM) and ultrastructural (electron microscopy). Electron microscopy proved useful for identifying transformations which were found to be specific for each chronological step considered: reduction of intracellular glycogen in clear cells and reduction of secretory granules in dark cells are typical signs of the first stage (3 h) after death; mitochondrial dilatation and rarefaction of cristae in clear and dark cells are typical of the second stage (6 h); rarefaction of microvilli in dark and clear cells is a sign of the last stage (12 h). Cytochemistry and immunohistochemistry supply useful information--not for all the chronological stage considered here, but for individual phases (3 h for hematoxylin-eosin and 6 h for alcian-PAS). However, it is particularly important to use the results from all such techniques simultaneously, so that the question of the exact time of death within the first 12 h post-mortem may be more accurately answered.

Primary leiomyosarcoma of the pulmonary artery: diagnostic and surgical implications.

Primary pulmonary trunk sarcoma is a rare and highly lethal disease. A case of multicentric pulmonary trunk leiomyosarcoma with right and left main pulmonary artery involvement, mimicking massive pulmonary embolism, is described. The importance of a timely diagnosis and of radical surgical excision is discussed.

Melanocyte-marker-HMB-45 is regularly expressed in angiomyolipoma of the kidney.

HMB-45 (melanocytic cell-specific monoclonal antibody) immunoreactivity was investigated in 10 cases of angiomyolipoma (AML) (1 with massive regional lymph node involvement) of the kidney and detected in all of them. No HMB-45 immunoreactivity was found in other tumors of the region which can occasionally be confused with AML, such as renal cell carcinoma, Wilms' tumor, and retroperitoneal sarcoma (leiomyosarcoma and liposarcoma). These findings indicate that HMB-45 is not a melanocyte-restricted marker and suggest that its expression might be useful in distinguishing AML from other tumors of the kidney and retroperitoneum.

Thyroid metastases from renal carcinoma.

The identification and diagnosis of thyroid metastases from renal adenocarcinoma are rare in living patients, though more frequent during autopsy. A case is reported in which the identification of thyroid metastases indicated a clear-cell renal carcinoma in a kidney treated 12 years earlier for emptying of multiple cysts.