Guido Monga

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).

Pattern of glomerular involvement in human immunodeficiency virus-infected patients: an Italian study.

Renal biopsy specimens from 26 adult human immunodeficiency virus (HIV)-infected patients with glomerular involvement were reviewed from the files of three hospital pathology services in Northern Italy. All the patients were Italian and most (19 of 26 patients) were intravenous drug addicts. The types of glomerular lesions were as follows: minimal-change glomerulopathy (two cases), mesangial proliferative glomerulonephritis (GN) with scanty immunoglobulin deposits (four cases), and various patterns of immune complex-mediated glomerulonephritis, including postinfectious GN (six cases), membranoproliferative GN (one case), membranous GN (three cases), immunoglobulin (Ig) A nephropathy (four cases), a mixed membranous and proliferative (three cases) and diffuse proliferative lupus-like pattern with subendothelial deposits, and intraluminal thrombi (two cases) or subepithelial and subendothelial deposits (one case). None of the patients had evidence of HIV-associated nephropathy. Our study confirms previous observations on the low incidence of HIV-associated nephropathy among white HIV-infected patients in Europe, where immune complex-mediated GN seems to predominate. Apart from the frequent electron microscopic observation of endothelial tubuloreticular structures, none of the reported lesions could be distinguished on morphologic grounds from those occurring in uninfected patients. The high variability of the glomerular lesions upholds the need for accurate diagnosis for the clinician confronted with an HIV-positive patient with suspected glomerular involvement.

Risk management of renal biopsy: 1387 cases over 30 years in a single centre

Backgroundu2003 Although renal biopsy is largely employed, even in old patients with systemic diseases, few clinical studies have addressed its risk management. We aimed to obtain a comprehensive assessment of safety/utility ratio of percutaneous renal biopsy.

Medullary carcinoma of the thyroid with atypical patterns

A case of a highly invasive thyroid carcinoma, which occurred in a 68‐year‐old woman, was studied by light and electron microscopy, and histochemical and biochemical analysis. Light microscopical, histochemical, and biochemical features were consistent with a diagnosis of a calcitonin‐producing, amyloidrich medullary carcinoma; electron microscopical patterns, mainly the presence of lumina, microvilli, and extensively dilated cytoplasmic E.R., were reminiscent of the ultrastructural features of the follicular carcinoma. Electrondense bodies interpreted as “secretory granules” were very scarce. This case appears very similar to the case recently presented by Valenta et al.48 and interpreted as a microfollicular carcinoma. The atypical features of our case of MCT seem to indicate that this tumor should be included in a group of atypical MCT; these should be kept separate from the typical (differentiated) ones on morphological, functional, and prognostic grounds.

Benign clear cell (‘Sugar’) tumor of the lung A light microscopic, histochemical, and ultrastructural study with a review of the literature

A case of a benign clear cell “sugar” tumor of the lung is reported. Light microscopy showed a uniform proliferation of clear cells filled with abundant glycogen. At the ultrastructural level, tumor cells were rich in free monogranular and rosette‐forming glycogen, but no membrane‐bound glycogen was demonstrated. Some cells showed plasma membrane interdigitations, microvilli, and macula occludens‐type junctions. Many polymorphic secretory and sporadic haloed neurosecretory‐like granules were observed, but argyrophil stains as well as a large set of immunohistochemical reactions specific for APUD derivation had negative results. A literature review of this puzzling entity with particular emphasis on the histogenetic hypotheses is presented, and a derivation from epithelial nonciliated bronchiolar (Clara) cells or epithelial serous cells is suggested.

Glomerulonephritis with organized deposits: A mesangiopathic, not immune complex-mediated disease? A pathologic study of two cases in the same family

Similar glomerular changes (marked widening of the mesangial stalk, irregular basement membrane thickening, and presence of mesangial and subendothelial deposits) were observed by light microscopy in renal biopsy specimens from two patients (mother and daughter) affected by nephrotic syndrome. Electron microscopy disclosed huge glomerular electron-dense deposits containing 12-nm fibrils in both patients. Immunohistochemical investigations performed with antisera anti-immunoglobulin (Ig) and anti-complement fractions, anti-laminin, anti-collagen IV, and anti-fibronectin (FN) showed scant and focal Ig and complement deposits and strong deposits of FN in the mesangium and along glomerular basement membranes. Most glomerular FN was plasma-derived, as shown by immunohistochemical tests with monoclonal antibodies specific for both plasma and cell-derived FN (IST-4) and for cell-derived FN (IST-9). Electron-dense deposits with fibrillar component could hardly correspond to the Ig and complement deposits, whereas they could be related to FN deposits. Since it is known that in glomeruli FN binds to Ig and immune complexes, and the latter seem to be too scant to justify light and electron microscopic lesions and clinical findings, the hypothesis of a primary mesangiopathic glomerulonephritis in some way connected with abnormal plasma FN deposition within the glomeruli and subsequent non-specific immune reactant entrapment could be considered. We could be dealing with a peculiar form of fibrillary glomerulonephritis with rather indolent evolution, as shown by a slow decrease of glomerular function and the scarcely modified glomerular changes found in the second biopsy performed in the mother 8 years after the first investigation.

Primitive neuroectodermal tumor of the meninges: An histological, immunohistochemical, ultrastructural, and cytogenetic study

We report a case of primitive neuroectodermal tumor (PNET) arising from the meninges in a 30-yr-old female patient whose clinical and radiological features were consistent with meningioma.The neoplasm was composed of primitive small, round cells, growing in sheets and nests in continuity with meningeal layers. Ultrastructurally, the neoplastic cells were characterized by large and regular nuclei, primitive cytoplasm with pools of glycogen, and lack of dense core granules. The neuroectodermal nature of the tumor was confirmed by positive immunostaining for vimentin, neurofilaments, neuron specific enolase (NSE), and 013 (an antibody raised against MIC2 antigen). Further support to the diagnosis was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) detection of Chromogranin A and Secretogranin II genes. t(11;22) translocation was also observed by RT-PCR, a finding that was not recorded in previously described intracranial PNET. The tumor followed a malignant course, recurring and spreading to chest wall and sacro-iliac region over a 10-yr period. The meningeal location enlarges the topographic spectrum of intracranial PNET, and this tumor has to be considered in the differential diagnosis with meningioma.

Glomerular findings in mixed IgG-IgM cryoglobulinemia

SummaryA case of immune-complex glomerulonephritis with membrano-proliferative patterns in a patient with mixed IgG-IgM cryoglobulinemia has been investigated; particular attention has been payed to histological, immunofluorescence, histochemical and electron microscopical findings in order to elucidate the nature of the intraluminal thrombi. The so called thrombi, strongly positive for IgG and IgM with the immunofluorescence, appeared to be clusters of mononuclear cells which, for their ultrastructural and histochemical (nonspecific esterase activity) patterns have been considered as monocytes. They showed cytoplasmic vacuoles containing microtubular structures; the latter have been detected free in the capillary lumina and in the basement membranes as well. These structures have been considered as the ultrastructural counterpart of the IgG-IgM immune-complexes responsible of the nephropathy. Monocytes have been hypotesized to play a pathogenetical role, acting as cleaners of the cryoprecipitate from the capillary lumina.

Light microscopic and immunohistochemical evaluation of vascular and neural invasion in colorectal cancer.

One hundred and sixty consecutive surgically removed colorectal carcinomas were investigated on histological sections stained with Hematoxylin and Eosin (H & E). Vascular and neural neoplastic invasion was found in 49 (30.6%) and 50 (31.3%) patients. In addition, immunohistochemical investigation was performed on step sections to those stained with H & E in the first 50 patients, using anti-human Factor VIII related antigen, anti-actin and anti-protein S 100 antisera. The percentages of positive cases for vascular invasion in this group of 50 patients were 20% on H & E sections and 62% on those stained with anti-Factor VIII and anti-actin antisera. Neural infiltration was identified in 14% of cases on H & E sections and in 70% of cases on anti-protein S 100 treated sections. Since vascular and neural infiltration are known to be ominous prognostic factors, their identification has great clinical relevance. The use of these simple immunohistochemical stains, using readily available antisera on formalin-fixed material, is recommended as routine procedure in surgical pathology laboratories.

Pattern of double glomerulopathies. A clinicopathologic study in nine nondiabetic patients.

Nine new cases of double glomerulopathies (GP) were found among 1,715 renal biopsies. Immunofluorescence and electron microscopy were needed to achieve a correct diagnosis and the prevailing relevance of these techniques in single cases was stressed. IgA nephropathy was the most commonly found GP, being associated with membranous glomerulonephritis (GN) (2 patients), minimal change disease (3 patients), and focal segmental glomerulosclerosis (1 patient). In addition, single cases of membranous GN plus crescentic GN and acute GN plus cryoglobulinemic GN were recorded. Possible factors involved in the pathogenesis and clinical significance of double glomerulopathies are discussed.