Gianluca Marucci

A case of hyperkeratosis follicularis et parafollicularis in cutem penetrans Kyrle's disease in a 41-year-old woman is described. It was a recurrence of a lesion surgically removed and originally diagnosed as invasive squamous cell carcinoma. Kyrle's disease is a rare dermatosis and should not be confused with neoplastic conditions i.e. squamous cell carcinoma. Pathologists should be aware of such conditions in order to avoid misdiagnosis, which can imply over treatment for the patient.

We describe a case of heterotopic mesenteric ossification presented in a 25 year-old male who underwent laparotomy for a fire-gun injury. Two weeks later he experienced small bowel obstruction and for this reason he has been operated five times with removal of segments of small bowel. Now, nine months later, he needs ileostomy to avoid another obstruction.

Rhabdomyosarcoma (RMS) is the most frequent sarcoma of infancy. Embryonal RMS is generally correlated with a better response to chemotherapy. In the present paper two cases of embryonal RMS of the orbit affecting adult patients are reported. Both patients are male, aged 22 and 24 years respectively. In Case 1 the lesion arose primitively in the orbit, in Case 2 the orbit was affected by secondary involvement. Both patients presented a rapid response to chemotherapy, with reduction of the neoplastic mass and regression of symptoms.

A case of ganglioneuroma arising within a cystic mature teratoma of the ovary in a 34-year-old woman is reported. Patient underwent right adnexectomy. The ovary was completely replaced by a bilocular cystic lesion, measuring 8 cm in diameter and filled with adipose tissue and pilosebaceous material. Microscopically the cyst was composed by a mature cystic teratoma containing skin with dermal appendages, fatty tissue and bronchial epithelium. Furthermore a nodule (0.5 cm in size) composed of mature ganglion cells, axons and Schwann cells, was identified. Ganglion cells were positive for NSE and synaptophysin, while Schwann cells stained positively with S100 protein and GFAP. To the best of our knowledgment this is the first reported cases of ganglioneuroma arisen within a cystic mature teratoma of the ovary.

We report two cases in which fine needle aspiration (FNA) in the breast generated changes histologically mimicking malignant lesions. In both cases a population of giant cells was present; the cells were osteoclast-like in the first case and 'atypical' multinucleated stromal giant cells in the second. The underlying lesion was pseudoangiomatous stromal hyperplasia (PASH) in both cases. The reactive nature was confirmed by retracing the needle tract and by the uneventful follow-up of 7 or 2 years, respectively. We propose that giant cell reaction be included in the list of FNA-generated changes.

The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR-181c-5p) th...

To assess the role of high sensitivity next-generation sequencing (NGS) of CTNNB1 for the diagnosis of adamantinomatous craniopharyngiomas (aCPs) and of BRAF for that of papillary CPs (pCPs) in routinely processed surgical samples of nonadenomatous sellar lesions. Forty-five cases of patients operated for nonadenomatous masses of the sellar region between 2004 and 2014 were retrieved from the files of the Anatomic Pathology unit of the Bellaria Hospital in Bologna, Italy. BRAF and CTNNB1 mutation status was analyzed by NGS in samples smaller than 1 cm(3) and histological re-evaluation was performed on all cases. CTNNB1 mutation analysis showed a sensitivity of 86.7 % and a specificity of 96.2 % for the diagnosis of aCPs. The specificity increased to 100 % considering that in one case, initially classified as a non-CP lesion (xanthogranuloma), the identification of a CTNNB1 S47R lead to histological re-evaluation and reclassification of the lesion as aCP. BRAF mutation analysis had a...

A case of CNS gliomyosarcoma, in a 71-year-old female with skeletal muscle differentiation is presented. The tumor was composed by two cell types: one showed features typical of glial cells, the other was constituted by elements having immunohistochemical positivity with desmin, sarcomeric actin, myoglobin and myogenin antisera. It is postulated an origin from a cell capable of dual differentiation.

Magnetic resonance imaging (MRI) is mandatory to identify the epileptogenic zone in refractory temporal lobe epilepsy (TLE). The correct identification of lesions is essential to obtain good post-surgery seizure control. Low grade tumours (LGT) and focal cortical dysplasia (FCD) are common findings in symptomatic TLE, and frequently coexist. The aim of this study was to identify the MRI characteristics in the diagnosis of FCD associated with LGT. We analyzed 24 subjects with TLE who underwent tailored surgery. They all had LGTs. Two expert neuroradiologists analyzed the imaging data and compared them with histological results, hypothesizing the causes of diagnostic errors in the identification of FCD. We selected three exemplary cases to report the most important causes of errors. In the diagnosis of FCD we reported false positives and false negatives due to different causes. An incomplete MRI protocol, the large dimensions of the tumour, infiltration and related oedema were the mos...

The quality control scheme in use at the Department of Anatomic Pathology of the University of Bologna-Bellaria Hospital Since 1993 a quality assurance (QA) scheme has been set up in our Department, modified from the protocol in use at the Department of Pathology of Yale University and published by J. Rosai in his textbook. A QA committee has been appointed and each member is responsible for a specific branch of the total workload; the areas involved are: 1. review of frozen section diagnoses with the final diagnoses 2. randomized review of biopsies (1:25) 3. quality control of cytological cases 4. quality control of specimen adequacy 5. quality control of immunohistochemistry and in situ Hybridization 6. quality control of the cytogenetics laboratory 7. quality control of autopsies All data collected from january 1996 to february 1999 have been reviewed and analyzed in order to provide references for other laboratories and for the purpose of monitoring our laboratory' performance.

The advent and widespread development of endonasal endoscopic techniques have recently expanded the frontiers of skull base surgery. The reduced invasiveness, wider and adjustable visualization of the operative field, and lack of postoperative cosmetic defects are well-known advantages of the endonasal endoscopic approaches compared with traditional surgical exposures both in adults and in children. The need to avoid disruption of facial growth centers and permanent tooth roots represents a further special consideration in favor of these endoscopic techniques in children. The authors report on a case of solitary myofibroma involving the ethmoid, mesial orbits, and anterior skull base with intracranial intradural expansion in a 17-month-old girl. The occurrence of such proliferative disease along the skull base is exceedingly rare. The tumor was successfully excised via an endoscopy-assisted cranionasal approach in which a transcranial microsurgical exposure was combined with endonasal endoscopic access to ensure a radical resection and optimize skull base reconstruction. To the authors' knowledge, the patient in this case is the youngest reported patient in the literature who has undergone treatment with this surgical strategy. The outcome in this patient underscores the feasibility and safety of endoscopic endonasal surgery even in toddlers and early childhood.

Temozolomide, an orally administered alkylating agent, is used to treat malignant gliomas. Recent reports also have documented its efficacy in the treatment of pituitary adenomas and carcinomas. Temozolomide methylates DNA and thereby exhibits an antitumor effect. O 6 ...

We report three cases of polymorphous adenocarcinoma (PLA) of the breast in 37-, 55- and 74-year-old women, respectively. The patients have no evidence of previous malignancy. The tumours consist of monotonous cells showing a wide spectrum of growth patterns: solid nests, trabeculae, tubules, cribriform structures, strands and fascicles reminiscent of polymorphous low-grade adenocarcinoma of salivary glands. To our knowledge, PLA

To present new information on the semiology and short-term evolution of seizures associated with primary brain tumors (PBTs) in a prospective study. This study is a section of the PERNO study--Project of Emilia Romagna Region on Neuro-Oncology, the main aim of which is to collect prospectively all cases of PBTs occurring in the Emilia-Romagna region, northeast Italy (3,983,346 population) from January 2009 to December 2011, to allow epidemiologic, clinical, and biomolecular studies. The epilepsy section of the PERNO study included all the patients who experienced seizures, either as first symptom of the tumor or appearing during the course of the disease. Each patient was interviewed by the referring neurologist with a specific interest in epilepsy. The patients who entered the study were followed up with visits on a quarterly basis. We collected 100 cases with full clinical, neuroradiologic, and pathologic data. The majority (79%) had high grade PBTs (glioblastoma in 50 cases), whereas the remaining patients had low-grade gliomas, mostly localized in the frontal (60%), temporal (38%), and parietal (28%) lobes. Seizures were the first symptom of the tumor in 72 cases. Overall, the initial seizures were tonic-clonic (48%) (without clear initial focal signs in more than half of the patients), focal motor (26%), complex partial (10%), and somatosensitive (8%). The majority of cases (60%) had isolated seizures or a low seizure frequency at the onset of the disease, whereas a high seizure frequency or status epilepticus was observed in 18% and 12% of cases, respectively. Ninety-two patients underwent surgical removal of the tumor, which was either radical (38%) or partial (53%). Seven patients underwent only cerebral biopsy. In the 72 patients in whom seizures were the first symptom, the mean time to the surgical treatment was 174 days, with a significant difference between high grade (95 days) and low grade (481 days) gliomas. At the time of our first observation, the majority of patients (69%) had already undergone surgical removal, with a mean follow-up of 3 months after the procedure. Overall, 39 patients (56%) were seizure free after tumor removal. The good outcome did not depend on presurgical seizure frequency or tumor type, although there was a trend for better results with low-grade PBTs. These data provide evidence that seizures are strictly linked to the tumoral lesion: They are the initial symptom of the tumor, reflect the tumor location and type, are usually resistant to antiepileptic treatment, and may disappear after the treatment of the lesion.

Glubran2 is a cyanoacrylate-based synthetic glue modified by addition of a second monomer. Among its many advantages over traditional cyanoacrylate products, Glubran2 has a much lower thermal polymerization temperature than that of cyanoacrylates used for cutaneous application. For many years, the new glue has been widely used in neuroradiology endovascular treatments. Our study aimed to assess the use of Glubran2 to treat possible complications arising during the embolization of aneurysms or vascular malformations like AVM or fistulae. A complication encountered in some of these cases is rupture of the vessel wall by the microguide or perforation of the aneurysmal sac by the coils used for embolization. This complication could be overcome by injecting Glubran2 into the rupture point but this would put the glue directly in contact with the subarachnoid space and possibly reach adjacent brain tissue. The aim of this experimental study was to place the glue in direct contact with brai...

OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushi...

Object In the last decade the indications for the endoscopic endonasal approach have been progressively expanded to include lesions that have not been traditionally considered amenable to resection through the transsphenoidal route. In this study, the authors analyze their experience with hypothalamic gliomas treated via the endoscopic endonasal approach. Methods Consecutive cases of hypothalamic gliomas treated since 2007 via an endoscopic endonasal approach were reviewed. Preoperative and postoperative neuroimaging as well as endocrinological, neurological, and visual symptoms were analyzed to assess the surgical outcome. Signs and symptoms of hypothalamic dysfunction including body mass index (BMI), memory, sleep-wake rhythm, and polyphagia were prospectively collected pre- and postoperatively to assess hypothalamic function. Quality of life was evaluated using the Katz scale. Results In the initial phase the endoscopic endonasal approach was adopted in 3 cases with a palliative intent, to obtain a biopsy sample or for debulking of the mass followed by radio- or chemotherapy. In 2 later cases it was successfully adopted to achieve gross-total tumor resection. Complications consisted of 2 postoperative CSF leaks, which required an endoscopic endonasal reintervention. Visual deficit improved in 3 cases and normalized in the other 2. Four patients developed diabetes insipidus, and 3 an anterior panhypopituitarism. All patients had a moderate increase in BMI. No patients presented with any other signs of hypothalamic damage, and their quality of life at follow-up is normal. Conclusions Despite the limitations of a short follow-up and small sample, the authors' early experience with the endoscopic endonasal approach has revealed it to be a direct, straightforward, and safe approach to third ventricle astrocytomas. It allowed the authors to perform tumor resection with the same microsurgical technique: dissecting the tumor with 2 hands, performing a central debulking, and controlling the bleeding with bipolar coagulation. The main limitations were represented by some anatomical conditions, such as the position of the chiasm and the anterior communicating artery complex and, finally, by the challenge of watertight plastic repair. To definitively evaluate the role of this approach in hypothalamic gliomas, a comparison with transcranial series would be necessary, but due to the rarity of these cases such a study is still lacking. The authors observed that more aggressive surgery is associated with a worse endocrinological outcome; thus they consider it to be an open question (in particular in prepubertal patients) whether radical removal is an advisable goal for hypothalamic gliomas.

Oncocytic meningioma is an uncommon variant of meningioma, characterized histologically by cells rich in mitochondria. This subtype of meningioma needs to be distinguished from other types of meningioma because of its more aggressive behavior. A case of oncocytic meningioma showing rapid clinical progression with diffuse intracranial dissemination after radiosurgery is described. Resistance to radiotherapy has been previously reported in oncocytic tumors of various body sites. This new case is a further example of the greater aggressiveness of oncocytic meningioma, suggesting that radiation therapy might worsen the course of disease.

A case of basaloid carcinoma of the pancreas in a 26-year-old woman is reported. The tumour was constituted by solid nests of relatively uniform neoplastic cells with hyperchromatic nuclei and scant cytoplasm, showing distinct peripheral palisading. There were necrotic areas and deposition of hyaline material, suggesting a basement membrane-like substance. Small foci of clear-cut squamous differentiation were present. Tumour cells were positive for cytokeratin 14 and P63 and negative for neuroendocrine and acinic cell markers. Ultrastructurally, the tumour was constituted by polygonal cells with round nuclei containing clumped chromatin. Occasional tight junctions and keratin filaments were present. Basaloid carcinomas may arise in several sites of the body, the most frequent being the anus and oesophagus, and have poor clinical outcome. The present case appears to be, to the best of our knowledge, the first documented example in the literature of basaloid carcinoma of the pancreas.

Object In the last decade the indications for the endoscopic endonasal approach have been progressively expanded to include lesions that have not been traditionally considered amenable to resection through the transsphenoidal route. In this study, the authors analyze their experience with hypothalamic gliomas treated via the endoscopic endonasal approach. Methods Consecutive cases of hypothalamic gliomas treated since 2007 via an endoscopic endonasal approach were reviewed. Preoperative and postoperative neuroimaging as well as endocrinological, neurological, and visual symptoms were analyzed to assess the surgical outcome. Signs and symptoms of hypothalamic dysfunction including body mass index (BMI), memory, sleep-wake rhythm, and polyphagia were prospectively collected pre- and postoperatively to assess hypothalamic function. Quality of life was evaluated using the Katz scale. Results In the initial phase the endoscopic endonasal approach was adopted in 3 cases with a palliative intent, to obtain a biopsy sample or for debulking of the mass followed by radio- or chemotherapy. In 2 later cases it was successfully adopted to achieve gross-total tumor resection. Complications consisted of 2 postoperative CSF leaks, which required an endoscopic endonasal reintervention. Visual deficit improved in 3 cases and normalized in the other 2. Four patients developed diabetes insipidus, and 3 an anterior panhypopituitarism. All patients had a moderate increase in BMI. No patients presented with any other signs of hypothalamic damage, and their quality of life at follow-up is normal. Conclusions Despite the limitations of a short follow-up and small sample, the authors' early experience with the endoscopic endonasal approach has revealed it to be a direct, straightforward, and safe approach to third ventricle astrocytomas. It allowed the authors to perform tumor resection with the same microsurgical technique: dissecting the tumor with 2 hands, performing a central debulking, and controlling the bleeding with bipolar coagulation. The main limitations were represented by some anatomical conditions, such as the position of the chiasm and the anterior communicating artery complex and, finally, by the challenge of watertight plastic repair. To definitively evaluate the role of this approach in hypothalamic gliomas, a comparison with transcranial series would be necessary, but due to the rarity of these cases such a study is still lacking. The authors observed that more aggressive surgery is associated with a worse endocrinological outcome; thus they consider it to be an open question (in particular in prepubertal patients) whether radical removal is an advisable goal for hypothalamic gliomas.

The optimal end point for phase II studies for recurrent glioblastoma (GBM) is unclear and a matter of debate. Moreover, data about post-progression survival (PPS) after the first disease progression in GBM patients treated according to EORTC 26981/22981/NCIC CE.3 trial are limited. The aim of this study was to evaluate the PPS in GBM patients. The analysis was made with a database on 1,006 GBM patients followed prospectively between 06/2005 and 06/2010. Eligibility criteria for the study were: age ≥18 years; PS: 0-2; chemotherapy given at disease progression after RT/TMZ. 232 patients (mean age 52 years, range 18-77 years) were enrolled. The median PFS following second line chemotherapy (PFS2) was 2.5 months (95 % CI 2.1-2.9) and the rate of patients free of progression at 6 months (PFS2-6 mo), was 21.6 % (95 % CI 16.3-26.9 %). The median PPS was 8.6 months (95 % CI 7.4-9.8), PPS rates were: PPS-6: 66 % (95 % CI 60.3-72.9 %), PPS-9: 48.2 % (95 % CI 41.5-54.9 %) and PPS-12: 31.7 % (95 % CI 25.2-38.2 %). PPS in unselected patients treated with alkylating agents is about 8 months. PPS rates could be of interest as an end point in future studies in recurrent GBM.

We describe a 69-year-old man with a non-small cell carcinoma of the lung, stage III B, who developed bilateral multiple erythematous lesions in the abdominal-inguinal area following treatment with gemcitabine. Histologically, the lesion was characterized by a heavy lymphocytic infiltrate with large CD30+ cells. The lesion was highly suggestive of cutaneous involvement by malignant lymphoma, but complete regression was observed after cessation of gemcitabine. Although rarely reported, gemcitabine therapy can induce skin lesions. Pathologists should be aware of this possibility in order to avoid a misdiagnosis.