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Medulloblastoma is an extremely rare disease in adults. After surgery, the mainstay of treatment is based on chemotherapy and radiotherapy, that provide 5 year suvival rates of 50-80% according to risk factors. Post-therapy nauronal maturation in medulloblastoma is a rare event that has been described only in pediatric age. Here we report the case of neuronal maturation after chemotherapy and radiotherapy in an adult patient. We also assessed that molecular SHH grouping with Illumina Human Methylation 450 k Bead Chip arrays showing that this molecular feature was stable during this maturation. We also discuss about treatment approaches in this rare situation.

The thyroid gland, from the Greek words thyreos (shield) and eidos(shape) is one of the largest endocrine organs, with a remarkable potential for growth and enlargement. Diseases due to altered parenchymal function and anatomic abnormalities of this gland are among the most common endocrine disorders in humans. Thyroid carcinoma is the most common endocrine malignancy, and both non neoplastic and neoplastic abnormalities are a frequent source of specimens for surgical pathology laboratories. Thyroid nodules are highly prevalent and often require cytopathologic evaluation. The general theme is that of the “needle in the haystack”: many are the thyroid nodules, few are those with malignant potential; of the malignant tumors, few are those that pose a significant threat for the patient life – although some of them, like anaplastic carcinoma, are among the most aggressive forms of human cancer. While most thyroid tumors are sporadic, a few develop in a familial setting or in the context of well-defined tumor syndromes (medullary carcinoma and MEN2 being the prototypical examples for C-cells, follicular carcinoma and Cowden syndrome for follicular cells). Some thyroid lesions pose considerable diagnostic challenges, and Dr. J. Rosai used to quote the words of the famous French pathologist C. L. Pierre Masson (one of the fathers of surgical pathology): “Of all cancers, thyroid epitheliomas teach, perhaps, the greatest lesson of humility to histopathologists”. Ancillary techniques, including immunohistochemistry and molecular diagnostics, may help resolve these difficult cases. What follows is an account of the relevant topics in the routine surgical pathology practice of the thyroid gland

Due to administrative changes involving the Institution, where the coauthors Matteo Zoli, Diego Mazzatenta, and Giorgio Frank are affiliated with, the authors have become part of the Institute of Neurological Sciences (of Bologna).

Background: The purpose of this study is to investigate the prognostic role of insulin-like growth factor receptor 1 (IGF1R) expression in surgically resected non-small-cell lung cancer (NSCLC). Patient characteristics and methods: This retrospective study was conducted in 369 stage I-II-IIIA, surgically resected, NSCLC patients. Patients exposed to anti-epidermal growth factor receptor (EGFR) agents were excluded. IGF1R expression was evaluated by immunohistochemistry in tissue microarray sections. Results: A positive IGF1R expression (score ≥ 100) was observed in 282 cases (76.4%) and was significantly associated with squamous cell histology (P = 0.04) and with grade III differentiation (P = 0.02). No difference in survival was observed between the positive and negative group when score 100 was used as cut-off for discriminating a positive versus a negative IGF1R result (52 versus 48 months, P = 0.99) or when median value of IGF1R expression was used (45 versus 55 months, P = 0.36). No difference in survival was observed between IGF1R-positive and -negative patients in a subgroup of stage I-II adenocarcinoma (n = 137) with known EGFR mutation and copy number status. Conclusions: IGF1R expression does not represent a prognostic factor in resected NSCLC patients. Patients with squamous cell carcinoma overexpress IGF1R more frequently than patients with nonsquamous histology, justifying the different sensitivity to anti-IGF1R agents observed in clinical trials

Follicular thyroid carcinoma (FTC) is a thyroid malignancy arising from follicular cells in which the diagnostic nuclear features of papillary thyroid carcinoma (PTC) are lacking. The lesions are usually encapsulated and show invasive growth

Some encapsulated follicular-patterned neoplasms of the thyroid pose diagnostic difficulties because of uncertainties whether the nuclear changes are sufficient to justify a diagnosis of papillary thyroid carcinoma (PTC) or because of uncertainties about the presence of capsular or vascular invasion.

Poorly differentiated thyroid carcinoma: a follicular-cell neoplasm that shows limited evidence of follicular cell differentiation, and occupies both morphologically and behaviorally, an intermediate position between differentiated (follicular and papillary carcinomas) and anaplastic carcinoma. The diagnostic histopathologic criteria of poorly differentiated thyroid carcinoma (PDTC) have been listed in the Turin consensus proposal

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): a non-invasive neoplasm of thyroid follicular cells with a follicular growth pattern and nuclear features of papillary carcinoma that has an extremely low malignant potential and shares these features with WDT-UMP

Tumors of uncertain malignant potential (UMP) are encapsulated or well-circumscribed follicular-patterned thyroid tumors with questionable capsular or vascular invasion, irrespective of presence or absence of papillary carcinoma-type nuclear features.

AIMS: Patients with colorectal cancer harbouring KRAS mutations do not respond to antiepidermal growth factor receptor (anti-EGFR) therapy. Community screening for KRAS mutation selects patients for treatment. When a KRAS mutation is identified by direct sequencing, mutant and wild type alleles are seen on the sequencing electropherograms. KRAS mutant allele-specific imbalance (MASI) occurs when the mutant allele peak is higher than the wild type one. The aims of this study were to verify the rate and tissue distribution of KRAS MASI as well as its clinical relevance. METHODS: A total of 437 sequencing electropherograms showing KRAS exon 2 mutation was reviewed and in 30 cases next generation sequencing (NGS) was also carried out. Five primary tumours were extensively laser capture microdissected to investigated KRAS MASI tissue spatial distribution. KRAS MASI influence on the overall survival was evaluated in 58 patients. In vitro response to anti-EGFR therapy in relation to different G13D KRAS MASI status was also evaluated. RESULTS: On the overall, KRAS MASI occurred in 58/436 cases (12.8%), being more frequently associated with G13D mutation (p=0.05) and having a heterogeneous tissue distribution. KRAS MASI detection by Sanger Sequencing and NGS showed 94% (28/30) concordance. The longer overall survival of KRAS MASI negative patients did not reach statistical significance (p=0.08). In cell line model G13D KRAS MASI conferred resistance to cetuximab treatment. CONCLUSIONS: KRAS MASI is a significant event in colorectal cancer, specifically associated with G13D mutation, and featuring a heterogeneous spatial distribution, that may have a role to predict the response to EGFR inhibitors. The foreseen implementation of NGS in community KRAS testing may help to define KRAS MASI prognostic and predictive significance.

Annalisa Altimari,1,* Dario de Biase,2,* Giovanna De Maglio,3 Elisa Gruppioni,1 Elisa Capizzi,1 Alessio Degiovanni,1 Antonia D'Errico,1 Annalisa Pession,2 Stefano Pizzolitto,3 Michelangelo Fiorentino,1,# Giovanni Tallini2,#1Laboratory of Molecular Oncologic and Transplantation Pathology, S. Orsola-Malpighi Hospital, Bologna, 2Laboratory of Molecular Pathology, Anatomic Pathology, Bellaria Hospital, Bologna, 3Department of Pathology, S. Maria della Misericordia Hospital, Udine, Italy*These authors contributed equally to this work #These authors share senior authorshipAbstract: Detection of KRAS mutations in archival pathology samples is critical for therapeutic appropriateness of anti-EGFR monoclonal antibodies in colorectal cancer. We compared the sensitivity, specificity, and accuracy of Sanger sequencing, ARMS-Scorpion (TheraScreen®) real-time polymerase chain reaction (PCR), pyrosequencing, chip array hybridization, and 454 next-generation sequencing to assess KRAS codon 12 and 13 mutations in 60 nonconsecutive selected cases of colorectal cancer. Twenty of the 60 cases were detected as wild-type KRAS by all methods with 100% specificity. Among the 40 mutated cases, 13 were discrepant with at least one method. The sensitivity was 85%, 90%, 93%, and 92%, and the accuracy was 90%, 93%, 95%, and 95% for Sanger sequencing, TheraScreen real-time PCR, pyrosequencing, and chip array hybridization, respectively. The main limitation of Sanger sequencing was its low analytical sensitivity, whereas TheraScreen real-time PCR, pyrosequencing, and chip array hybridization showed higher sensitivity but suffered from the limitations of predesigned assays. Concordance between the methods was k = 0.79 for Sanger sequencing and k > 0.85 for the other techniques. Tumor cell enrichment correlated significantly with the abundance of KRAS-mutated deoxyribonucleic acid (DNA), evaluated as ΔCt for TheraScreen real-time PCR (P = 0.03), percentage of mutation for pyrosequencing (P = 0.001), ratio for chip array hybridization (P = 0.003), and percentage of mutation for 454 next-generation sequencing (P = 0.004). Also, 454 next-generation sequencing showed the best cross correlation for quantification of mutation abundance compared with all the other methods (P < 0.001). Our comparison showed the superiority of next-generation sequencing over the other techniques in terms of sensitivity and specificity. Next-generation sequencing will replace Sanger sequencing as the reference technique for diagnostic detection of KRAS mutation in archival tumor tissues.Keywords: colorectal cancer, targeted therapy, KRAS mutations, next-generation sequencing, real-time polymerase chain reaction, pyrosequencing

Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26% (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. CONCLUSIONS: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.