Marzio Gabrielli

Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas

To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene‐containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients. Overall, eight angiomyolipomas, eight giant cell astrocytomas, one cortical tuber, and three rhabdomyomas were analyzed. Loss of heterozygosity at either TSC locus was found in a large fraction of the informative patients, both sporadic (7/14) and familial (1/4). Interestingly, a statistically significant preponderance of loss of heterozygosity at TSC2 was observed in the sporadic group (P < 0.01). Among the possible explanations considered, the bias in the selection for TSC patients with the most severe organ impairment seems particularly appealing. According to this view, a TSC2 defect might confer a greater risk for early kidney failure or, possibly, a more rapid growth of a giant cell astrocytoma. None of the seven antioncogenes tested showed loss of heterozygosity, indicating that the loss of either TSC gene product may be sufficient to promote hamartomatous cell growth. Finally, the observation of loss of heterozygosity at different markers in an astrocytoma and in an angiomyolipoma from the same patient might suggest the multifocal origin of the second‐hit mutation. Genes Chromosom Cancer 15:18–25 (1996).

Comparison of the results of immunocytochemical assays for biologic variables on preoperative fine‐needle aspirates and on surgical specimens of primary breast carcinomas

Fine‐needle aspiration biopsy (FNAB) is a well‐documented procedure for the diagnosis and biologic characterization of breast carcinoma. In order to compare the immunocytochemical expression of biologic parameters on cytology and on histology, estrogen receptor (ER) and progesterone receptor (PgR) status, p53 protein expression, and Ki67 growth fraction were evaluated on presurgical fine‐needle aspirates (FNAs) from breast carcinoma patients and on the corresponding surgical samples prior to any systemic therapy.

Fatal hepatic vascular toxicity of DTIC. Is it really a rare event

A fatal massive hepatic necrosis with widespread thrombotic occlusion of the small hepatic veins developed in two of 68 patients treated with DTIC for advanced melanoma in a randomized study. Thirteen similar reactions, in patients treated with single‐agent DTIC, are reported in the literature. Several clinical and pathologic features distinguish this DTIC toxicity from Budd‐Chiari syndrome and veno‐occlusive disease (both well‐known types of possibly drug‐related hepatic vascular disease) and make it a distinctive syndrome. We were impressed by the repeated occurrence of this complication in a relatively small set of patients, in contrast with the rarity of the literature reports. We suggest that this dramatic complication could occur more frequently than commonly thought. Therefore, caution should be used with DTIC, particularly in curable patients.

Melanotic neuroectodermal tumour of infancy (MNTI). Immunohistochemical and ultrastructural study of a case.

A case of melanotic neuroectodermal tumour of infancy (MNTI) which occurred in the left lower jaw of a 15-months old child was studied by electron microscopy and immunohistochemical methods to verify the neural crest origin of this tumour. Two cell population were observed: pigment melanocyte-like cells and non-pigmented nerve-like cells. Immunohistochemical analysis with neuron-specific enolase (NSE) and S-100 protein visualized two cell subtypes in the non-pigmented cell population. The combined ultrastructural findings and immunohistochemical data confirm the neural crest origin of MNTI.

Cutaneous hyperpigmentation induced by amiodarone hydrochloride

Amiodarone (Cordarone) is an iodinated compound widely used in the treatment of cardiac arrhythmias for more than a decade. A patient who developed a persistent blue-gray skin pigmentation of the light-exposed areas following long-term amiodarone hydrochloride administration is reported. The cutaneous signs and the ultrastructural findings are described. This rare iatrogenic hyperpigmentation is peculiarly due to lipofuscin and not melanin deposits. Its pathogenesis may be related to the basic action of the drug on the lysosome and to the extra phototoxic-induced lysosomal damage, which accounts for the specific location of the hyperpigmentation over the light-exposed areas.

Mandibular leiomyoma in an infant. Report of a case.

A case of mandibular leiomyoma in a 8-month-old baby is reported. This is the 5th case of intrabony leiomyoma of the jaws reported so far. The tumor presented as a symptomless swelling of the mandibular ramus and required a limited resection. The pertinent literature is reviewed and the histological features discussed.

Applicability of the bethesda system 2001 to a public health setting

The degree of applicability of the Bethesda System 2001 (TBS 2001) for cervicovaginal cytology to a public health setting is unknown, and extrapolations from available data are unwarranted.