Different patterns of p16INK4a immunohistochemical expression and their biological implications in laryngeal squamous cell carcinoma.

INTRODUCTION: p16INK4a immunohistochemistry (IHC) is widely used to facilitate the diagnosis of human papillomavirus (HPV)-associated neoplasia, when ≥70% of cells show strong nuclear and cytoplasmic positivity. In this study, we aim to compare partial expression patterns that do not fulfill the above criteria and seek biological implications in laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: p16INK4a IHC staining was conducted on representative sections of archived tissue from 88 LSCCs. Immunoreactivity was described based on four parameters: intracellular localization of immunostaining, intensity of immunostaining, distribution pattern and percentage of positive cells. RESULTS: Six patterns of p16INK4a immunoexpression were observed and defined as: strong diffuse (strong immunostaining, expression in cytoplasm and nucleus in >70% of tumor cells), weak diffuse (moderate or weak immunostaining, expression in cytoplasm in >70% of tumor cells), marginal (strong cytoplasmic immunostaining, limited to the periphery of tumor islets), strong scattered (strong immunostaining, expression in cytoplasm and nucleus in <50% of tumor cells), weak scattered (moderate or weak immunostaining, expression in cytoplasm in <50% of tumor cells), negative (no expression). The pN stage of the patients was associated with p16INK4a immunoexpression patterns, the marginal pattern was only found in the pN0-Nx stages, while the weak diffuse pattern was more frequently observed in pN2-N3 stages. CONCLUSIONS: Partial immunostaining with architecturally distinct p16INK4a immunoexpression patterns may prove significant in stratifying characteristic clinicopathological subgroups among LSCC. Our observations may support the hypothesis that p16INK4a has different roles in different subcellular locations, with tumorigenic molecular pathways unrelated to HPV infection.

Could oral cytomorphometry be of value in distinguishing diabetes mellitus?

The present study refers to a quantitative, morphometric analysis of exfoliative cytology smears collected from diabetes mellitus (DM) patients, in order to distinguish subtle changes in cellular and nuclear parameters. The study was carried out on 30 adult subjects: a control group of 10 healthy subjects and a study group of 20 diabetic subjects (type 1 and type 2 DM). Another factor that was taken into consideration was the abundance of the microbial flora. The oral smears were stained using Hematoxylin and Eosin and several parameters were measured (nuclear diameter, perimeter and area, cell large diameter and area), and calculated: nuclear/cytoplasmic ratio and nuclear roundness factor. We found out that the cells collected from DM patients had higher values of the nuclear parameters (the nuclei were larger) and lower cell dimensions. The nuclear to cytoplasmic ratio was increased in these patients, but the nuclear roundness factor was closer to one in the study group. Also, an increased number of bacteria, often seen in DM patients, decreased the nuclear parameters. Our findings complete recently descriptive cytology studies with the morphological measurements in case of bacterial abundance and sustain the possible value as screening method for morphometry.

The value of exfoliative cytology in the diagnostic of oral mucosa changes in diabetes mellitus.

In this study, we performed microscopic qualitative analyses of the oral epithelium cytological smears in potential early phase of diabetes and in type 1 and 2 diabetic patients versus a healthy control group. The cytological assessment of the oral changes was realized on superficial and profound smears, from jugal and ventral tongue mucosa and it was based on the comparison between three staining methods [Papanicolaou, APT (polychrome tannin blue)-Dragan and Hematoxylin-Eosin (HE)]. Cytological changes of oral cells population were correlated with the type, duration and complications of diabetes. Oral flora was also evaluated. Irrespective the staining used, we found a clear dividing line between the control group and the real diabetic patients. In all diabetes cases (independently of the type of smear, harvest site, clinical form of disorder and present complications), cells presented alterations both at the level of cytoplasm and nucleus. Dyschromasia, cytolysis, different degrees of fatty degenerescence, binucleated cells, hyperchromasia, nuclear enlargement with modified nuclear÷cytoplasmic ratio, were the most frequent findings. There were no discrepancies in the cellular aspects of type 1 or 2 diabetic patients' smears or between the control group and the potential prediabetic status patients. Findings were interpreted as oral epithelium reactive changes induced by the disease. We concluded that exfoliative cytology alone is of low value as a diagnostic and prognostic tool in the diagnosis of diabetes mellitus (DM); it detects the reactive changes induced by the disease, but it makes no differences between DM types or degree of severity and does not allow by qualitative analysis alone to detect abnormalities in early diabetes.

Intracranial immature teratoma with a primitive neuroectodermal malignant transformation - case report and review of the literature.

INTRODUCTION: Central nervous system (CNS) germ cell tumors are very rare, accounting for 0.3-3% of primary intracranial neoplasms; of these, the teratomas are even more uncommon. The immature variant of teratomas, defined by the presence of incompletely differentiated components resembling fetal tissues is considered as having a low, almost borderline malignancy state. CASE PRESENTATION: A 35-year-old male presented with a left fronto-basal tumor. At surgery, a grey white tumor, mostly solid, was excised. The histopathological examination revealed an infiltrating teratoma. The histological spectrum varied from epithelial and mesenchymal mature to immature tissues. These structures were intimately mixed with significant areas of primitive neuroepithelial tubules and÷or primitive neuroectodermal tissues. The diagnosis was that of an immature intracranial teratoma, with high histological grade WHO (World Health Organization) (Norris grade III). After surgical resection, a rapid infratentorial contralateral subarachnoid extension followed. The second tumor was largely formed by primitive neuroectodermal tumor (PNET)-like structures and rare mature epithelial tissues, meaning a PNET-like overgrowth or "malignant transformation" of an immature teratoma. After specific oncological treatment, the patient had a favorable evolution with no signs of relapse (2016). CONCLUSIONS: The present case highlights the value of the Norris grading system (mostly used in grading ovarian immature teratomas) in a very rare case of intracerebral immature teratoma with rapid subarachnoid extension caused by an unexpected secondary "malignant transformation".

Pediatric glioblastoma with giant cells and "supratentorial" primitive neuroectodermal component - case report and review of the literature.

INTRODUCTION: The glial differentiation in pediatric "supratentorial primitive neuroectodermal tumors" (sPNET) is occasionally revealed by immunohistochemistry with GFAP (glial fibrillary acidic protein) as isolated positive cells among undifferentiated cells, indicative of divergent cellular phenotypes. Large malignant glial tumors in sPNETs are extremely rare and challenge the neuropathologist by raising the possibility of glioblastomas with sPNET-like features (GB sPNET). The distinction between them is important because of their different treatment and prognostic. CASE PRESENTATION: A large parieto-occipital tumor with minimal ventricular invasion, in an 11-year-old girl, with a five-month clinical history, was proven to be a highly malignant biphasic tumor, consisting in a glioblastoma with giant cells, representing 75% of the tumor, and sPNET nodules, with one larger dominant nodule. The immunohistochemistry confirmed positivity for synaptophysin, neurofilament, neuron-specific enolase and CD56 in the sPNET compartment and for GFAP, CD56 and vimentin in the glioblastoma. In some parts of the tumor, the two components were well delineated from each other as in a "collision" tumor, but in others, the two different tumors were intermingled. It was histologically diagnosed as sPNET with double differentiation (glial and neural) or glioblastoma with sPNET-like features. CONCLUSIONS: These cases are very rare, few reported, especially in the pediatric population, and with high difficulties in histological differential diagnosis, subsequently reflected in the therapeutic decisions.