Adele Caldarella

Immunohistochemistry is highly sensitive and specific for the detection of NRASQ61R mutation in melanoma.

Testing for NRAS is now integral part in the assessment of metastatic melanoma patients because there is evidence that NRAS-mutated patients may be sensitive to MEK inhibitors, and RAS mutation is a common mechanism of acquired resistance during treatment with BRAF inhibitors. This study evaluated the sensitivity and specificity of immunohistochemical analysis using an N-Ras (Q61R) antibody to detect the presence of the NRASQ61R mutation in melanoma patients. A total of 98 primary cutaneous melanomas that have undergone examination of NRAS mutation were retrieved from a multicentric database. Formalin-fixed and paraffin-embedded melanoma tissues were analyzed for BRAF and NRAS mutations by independent, blinded observers using both conventional DNA molecular techniques and immunohistochemistry with the novel anti-human N-Ras (Q61R) monoclonal antibody (clone SP174). The antibody showed a sensitivity of 100% (14/14) and a specificity of 100% (83/83) for detecting the presence of an NRASQ61R mutation. Of the NRAS-mutated cases, none of the non-Q61R cases stained positive with the antibody (0/7). There were three cases with discordant NRAS mutational results. Additional molecular analysis confirmed the immunohistochemically obtained NRAS result in all cases, suggesting that a multiple analytical approach can be required to reach the correct sample classification. The reported immunohistochemical method is an accurate, rapid, and cost-effective method for detecting NRASQ61R mutation in melanoma patients, and represents a valuable supplement to traditional mutation testing. If validated in further studies, genetic testing would only be required for immunohistochemistry-negative patients to detect non-Q61R mutations.

Long-term survival, prevalence, and cure of cancer: A population-based estimation for 818,902 Italian patients and 26 cancer types

Original, population-based estimates of indicators of long-term survival and cure in cancer patients are provided. More than a quarter of cancer patients in Italy have reached death rates similar to those of the general population. Nearly three quarters of them will not die as a result of cancer. These estimates are potentially helpful to health-care planners, clinicians, and patients.

The thickness of melanomas has decreased in central Italy, but only for thin melanomas, while thick melanomas are as thick as in the past.

The objective of this study was to evaluate the time trend of melanoma thickness in a population-based case series. All invasive (n=2862) and in-situ (n=605) cutaneous melanoma incident cases diagnosed in 1985–2004 were retrieved from the Tuscany Cancer Registry, central Italy. Standardized (European population) incidence rates were computed for four periods: 1985–1989, 1990–1994, 1995–1999, 2000–2004, and for Breslow thickness classes (≤1, 1.01–2.00, >2 mm). The annual percent change (APC) of the standardized rates was computed. Thickness was evaluated on the basis of sex, age, morphology type, site and period of time. Median thickness was evaluated by means of a nonparametric K-sample test. The incidence rate of melanoma rose significantly for both invasive (APC=+5.1%) and in-situ lesions (APC=+11.1). The sex distribution of patients with invasive melanoma did not change over time (mean male/female ratio 0.95). The mean age at diagnosis did not change (57.2 years; SD=17.2 years). From 1985–1989 to 2000–2004 the median value of thickness decreased from 1.68 to 0.8 mm (P<0.001). Within the Breslow categories the median value of thickness decreased significantly for thin melanomas (≤1 mm) but not for intermediate (1.01–2.00) or for thick melanomas (>2 mm). Among the most common melanoma types, the median thickness decreased for superficial spreading melanomas but not for nodular melanomas. Over time, the incidence of melanoma has increased notably and the median thickness has decreased. However, median thickness has decreased only among thin melanomas, whereas it has not changed for thick melanomas, most of which are of the nodular type.

Brain Heterotopia in Pharyngeal Region. A Morphological and Immunohistochemical Study

Pharyngeal brain heterotopia is a congenital and generally biologically benign lesion. In contrast to brain heterotopia in the nose, the most common site of this lesion, brain heterotopia in the pharynx is very rare. Pharyngeal heterotopic tissue can be composed of various components, i.e., astrocytes, neurons, ependyma or choroid plexus, oligodendrocytes, retina, and, occasionally, neoplastic nodules. In contrast, nasal lesions are often only composed of astrocytes. We report a case of brain heterotopia in the pharyngeal region, diagnosed in a newborn female infant, causing serious respiratory distress. The infant underwent surgical excision of the lesion, and after 1 year of follow-up, she is recurrence-free. The mass, about 3 cm in diameter and showing no connection with encephalic structures, was characterized by numerous papillary structures and areas containing stellate-like or spindle cells focally forming nodules. Moreover, there was inflammatory infiltration, whereas mitoses, hemorrhages, and necroses were absent. Immunohistochemistry revealed a choroid plexus nature of the papillary formations (S-100, cytokeratins, transthyretin and vimentin-positive) and the presence of glial and neuronal cells in the remaining areas (glial fibrillary acidic protein, neuron-specific enolase, neurofilaments, synaptophysin, and S-100 positive). This case report confirms that the presence of choroid plexus is not uncommon and that pharyngeal brain heterotopia is usually benign.

Cerebellar liponeurocytoma : Morphological, immunohistochemical, and ultrastructural study of a relapsed case

Cerebellar liponeurocytoma is a rare and newly identified neoplasm  found  in  adults  which  is  reputed  to  be benign. Its salient morphological characteristics are advanced neuronal/neurocytic differentiation, the presence of lipomatous areas, low mitotic rate, and the absence of necrosis, pleomorphism and vascular hyperplasia. Reported is a case of relapsing liponeurocytoma which occurred 3 and a half years after the radical excision of the primary lesion. Histopathological aggressive features (mitoses and a high proliferation index as evaluated by MIB‐1) were shown in the primary lesion and recurrence of the tumor. We suggest that liponeurocytoma is an uncertain malignant potential lesion when mitoses are present and the MIB‐1 positive cells are more than 10%.

Cerebellar Liponeurocytoma: Immunohistochemical and Ultrastructural Study of a Case

The clinical, histopathological, and ultrastructural features of a cerebellar liponeurocytoma are reported. The tumor, a 3-cm mass localized in the right cerebellar hemisphere, was resected from a 61-year-old man clinically presenting with symptoms of intracranial hypertension. The lesion was composed of small, in some areas closely packed, medulloblastoma-like cells with prominent areas of lipidization phenomena. Moreover, mitoses, cellular atypia, and numerous vascular structures were focally observed. Glial and neuronal differentiation was immunohistochemically noted (glial fibrillary acidic protein, synaptophysin, neurofilaments, and neuron-specific enolase positivity). The p53 oncoprotein was detected in the majority of neoplastic cells and a moderate proliferation activity, evaluated by Mib-1 antibody, was focally appreciated. Ultrastructural study did not show evident neuritic processes, synapses, or dense core neuroendocrine granules. This cerebellar tumor previously called lipidized medulloblastoma and recently renamed cerebellar liponeurocytoma is considered an adult neoplasm with excellent prognosis histologically presenting prominent lipidized areas and, at the immunohistochemical and ultrastructural level, both glial and neuronal differentiation. The present study providesthe first description of a less differentiated and histologically more aggressive form of this unusual tumor.The clinical, histopathological, and ultrastructural features of a cerebellar liponeurocytoma are reported. The tumor, a 3-cm mass localized in the right cerebellar hemisphere, was resected from a 61-year-old man clinically presenting with symptoms of intracranial hypertension. The lesion was composed of small, in some areas closely packed, medulloblastoma-like cells with prominent areas of lipidization phenomena. Moreover, mitoses, cellular atypia, and numerous vascular structures were focally observed. Glial and neuronal differentiation was immunohistochemically noted (glial fibrillary acidic protein, synaptophysin, neurofilaments, and neuron-specific enolase positivity). The p53 oncoprotein was detected in the majority of neoplastic cells and a moderate proliferation activity, evaluated by Mib-1 antibody, was focally appreciated. Ultrastructural study did not show evident neuritic processes, synapses, or dense core neuroendocrine granules. This cerebellar tumor previously called lipidized medulloblastoma and recently renamed cerebellar liponeurocytoma is considered an adult neoplasm with excellent prognosis histologically presenting prominent lipidized areas and, at the immunohistochemical and ultrastructural level, both glial and neuronal differentiation. The present study provides the first description of a less differentiated and histologically more aggressive form of this unusual tumor.

Melanoma survival: sex does matter, but we do not know how.

The objective of this study was to provide further insights into the prognostic role of female sex in skin melanoma. The prognostic effect of sex in a population-based case series of 3900 skin melanomas in central Italy has been evaluated considering the possible confounding role of many demographic and clinical variables (age, period of diagnosis, Breslow’s thickness, Clark level, ulceration, lymph node status, metastasis, histological type, skin site, and pathological T and N). Multiple imputations, according to chained equations, have been used for imputing incomplete values. A Cox proportional hazards model on the risk of death caused by melanoma was fitted. Univariate and multivariate effects of sex and of other variables were computed. The 5-year cause-specific survival was 87% (95% confidence interval: 86–89%) for women and 80% (78–82%) for men. Women had higher rates at any time since diagnosis. After adjustment for other confounders, women had a 34% reduced risk compared with men of dying from skin melanoma (hazard ratio=0.66, 95% confidence interval: 0.56–0.79). The present study confirmed a strong protective effect of female sex on skin melanoma mortality. The protective factor is still unknown.

Is the incidence of brain tumors really increasing? A population-based analysis from a cancer registry

Recently, an increasing incidence of brain tumors has been reported from multiple studies. Brain tumors diagnosed in the period 1985–2005 were identified through the Tuscan Cancer Registry, a population-based registry active since 1985 in the area of Florence and Prato. Age-standardized incidence rates and average annual percent change (APC) was calculated for the entire period from 1985 to 2005 for sex and behavior. A total of 4,417 brain tumors was registered, 1,900 (43%) in male and 2,517 (57%) in female patients. Malignant and benign tumor incidence rates were 8.3 and 4.1, respectively, among males and 6.4 and 7.2, respectively, among females. The age-adjusted annual incidence rate of all brain tumors was 13.9, with a statistically significant increasing rate throughout the period (APC: +3.2, CI 2.2–4.2). The annual incidence rate remained stable for malignant brain tumors but increased significantly for benign brain tumors (APC: +6.2, CI 4.5–7.9). In our population-based study, the incidence of brain tumors increased from 1985 to 2005 overall and for benign tumors, but not for malignant tumors. Part of the temporal variations may be attributed to improvement in diagnostic imaging techniques and, particularly for benign tumors, in changes in registration practice.

Oncocytic meningioma: A case report

Oncocytic meningioma is a recently described rare variant of meningothelial neoplasms that typically occurs as a large cell tumor with granular cytoplasm. The distinct histological features of numerous cells with granular cytoplasm and the ultrastructural evidence of numerous mitochondria in the cytoplasm differentiate this tumor from other neoplasms with granular appearance. We report an additional case of oncocytic meningioma investigated by ultrastructural and immunohistochemical methods.

Cyclooxygenase-2 in oligodendroglioma: Possible prognostic significance

Cyclooxygenase‐2 (COX‐2) is the inducible form of the enzyme involved in the first two steps of the prostaglandins and thromboxane synthesis. Up‐regulation of COX‐2 is demonstrated in tumors where it can modulate tumoral progression, metastasis, multidrug resistance and angiogenesis. Selective COX‐2 inhibitors are seen with growing interest in the tumors treatment. This present study reviews the COX‐2 expression in 32 primary oligodendrogliomas (24 WHO II; eight WHO III) and two glioblastomas with prominent oligodendroglial features (WHO IV). Immunohistochemical results were compared with survival in order to verify the COX‐2 prognostic significance. COX‐2 positivity was found in 44% tumors. Median survival of the patients with a COX‐2 positive lesion was 37 months; median survival of the patients with a COX‐2 negative lesion was 93 months (P = 0.010). Twenty‐nine percent WHO grade II tumors, 87% WHO grade III, 50% WHO grade IV resulted COX‐2 positive (P = 0.016). In patients affected by WHO grade II oligodendroglioma, median survival was 24 and 96 months, respectively, in COX‐2 positive and negative lesions (P = 0.012). In conclusion, even if further studies on different, homogeneous and larger series in vivo are certainly necessary, it is believed that COX‐2 could really have a prognostic value and can be considered as a possible therapeutic opportunity.