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The development of chemoresistance in a variety of cancers seems related to overexpression of the P-glycoprotein (P-gp) drug pump. Nephroblastoma, the most common malignant renal tumor of childhood, usually is responsive to treatment, and prognosis is favorable in most cases. However, the disease in a subset of patients is refractory to treatment, and the disease follows an aggressive course. To study P-gp expression in this tumor and its correlation with outcome, tumor samples from 93 patients were examined by immunohistochemical analysis. P-gp expression was determined separately in both tumor cells and intratumoral capillary endothelium. The likelihood ratio test, the Kaplan-Meier method, and the log-rank test were used to evaluate its association with clinical course, grade, stage, and administration of preoperative chemotherapy. The results for the majority of nephroblastomas were variably positive; in 43 (46%) of them, newly formed capillary endothelial cells also stained positive. While no association of P-gp expression in tumor cells with clinical course, stage, and grade could be demonstrated, positivity in endothelial cells correlated significantly with unfavorable outcome, suggesting that chemoresistance depended on an active blood-tumor barrier. Previous chemotherapy induced P-gp overexpression in tumor cells.

Glomerulocystic kidney disease (GCKD) is a rare congenital condition that is usually reported in infants and young children. Only five cases of acquired GCKD after an acquired renal disease have been reported. Among these, two patients have developed cystic glomerular lesions following hemolytic uremic syndrome (HUS). We report a third case in a 2-year-old patient with this association. Common features between these three cases include atypical HUS, development of GCKD after prolonged peritoneal dialysis treatment, severe hypertension, and normal-sized kidneys without development of macroscopic cysts. Pathology findings in our patient include heavy expression of epidermal growth factor receptor in proximal tubules and evidence of obstruction of the glomerular outflow. We speculate that cystic dilatation of the Bowman's capsule may be secondary to ischemic lesions leading to proximal tubular obstruction.

Using morphometry and image analysis, we investigated 17 patients showing intestinal pseudo-obstruction secondary to intestinal neuronal dysplasia (IND) and 20 controls. In addition to an increase in the number and size of the ganglia and the ganglionic cells, we also noted a significant increase in NO synthase-containing ganglionic cells. We found that this enzyme, responsible for the synthesis of nitrous oxide caused by oxidation of L-argynine aminoacid, is a neurotransmitter able to induce smooth muscle relaxation by activating cyclic AMP. If the increase in NO synthase-producing ganglionic cells is responsible for the increase in nitrous oxide production, one can hypothesize that an overproduction of nitrous oxide plays a role in the pathogenesis of intestinal pseudo-obstruction secondary to neuronal dysplasia. As NO synthase can be blocked, as was demonstrated by giving L-methil-arginine or N-G-nitro-L-argynine, it might be possible to treat intestinal pseudo-obstruction caused by intestinal neuronal dysplasia at the pharmacological level.

Osteoclasts from a patient affected by osteopetrosis were examined in vivo and in vitro. Iliac crest biopsy revealed an osteosclerotic pattern, with prominent numbers of osteoclasts noted for hypernuclearity and incomplete adherence to the bone surface. A population comprising tartrate-resistant acid phosphatase (TRAP)-positive, multinucleated and mononuclear cells, and alkaline phosphatase-positive stromal fibroblasts was obtained in vitro from bone marrow. Mononuclear TRAP-positive precursors spontaneously fused in culture to form giant osteoclast-like cells. These cells expressed the osteoclast marker MMP-9 and calcitonin receptor, and lacked the macrophage marker, Fc receptor. Expression and distribution of c-src, c-fms, and CD68, and response to steroid hormones relevant to osteoclast differentiation and function were apparently normal, whereas cell retraction in response to calcitonin was impaired. TRAP-positive multinucleated cells did not form osteoclast-specific adhesion structures (clear zone, podosomes, or actin rings). Bone resorption rate was severely reduced in vitro. Focal adhesions and stress fibers were observed en lieu of podosomes and actin rings. Adhesion structures contained low levels of immunoreactive vitronectin receptor, most of this integrin being retained in cytoplasmic vesicles. These data provide the first characterization of abnormal differentiation and function of human osteopetrotic osteoclast-like cells.

Sinus histiocytosis with massive lymphadenopathy (SHML) (Rosai-Dorfman disease) is a rare self-limited histiocytic disorder of unknown origin, usually present with cervical lymphadenopathy, fever, elevated ESR and haematologic abnormalities. Extranodal lesions may occur as initial manifestations of the disease. In most cases skin lesions are associated with nodal or extranodal localization. A 54-year-old male is reported who, for a period of ten months, presented numerous slowly enlarging, rounded papular lesions on the face, neck, trunk as well as severe cervical lymphadenopathy without general and haematological disturbances. Thereafter a fungating mass developed in the nasal cavity. Histological, histochemical and immunohistochemical tests of skin, mucosal and lymph-node lesions were consistent with a diagnosis of SHML. The immunohistochemical characterization of the cytophagocytic S-100+ macrophages revealed that they were highly positive for the adhesion molecules Vitronectin receptor av/b3, which is used by tissue macrophages for removal of effete cells through phagocytosis.

Myofibroblastoma (MF) is an uncommon, usually benign, mesenchymal tumor infrequently described in soft tissues. We report here on the clinicopathologic findings of a soft tissue MF (STMF) presenting in the neck of a 90-year-old man as a slowly growing and non-painful nodule, 4 cm in greatest diameter. Histology revealed a circumscribed lesion constituted of monomorphous bipolar spindle cells arranged in swirling fascicles with intervening broad bands of hyalinized collagen and well formed “amianthoid” fibers. Immunohistochemistry showed the spindle cells to be immunoreactive for vimentin, smooth muscle actin and muscle specific actin and, focally, for desmin; im-munostaining for cytokeratin, epithelial membrane antigen, S-100 protein, factor VIII-related antigen, and CD34 was negative. Based on the present case and on those previously reported in the literature, STMF is characterized by: 1) exclusive incidence in the male sex; 2) variable immunoreactivity of the neoplastic cells for desmin, probably reflecting an origin from a peculiar subset of myofibroblasts, or, alternatively, a further myoid differentiation; 3) variable abundance of (hyalinized) collagen; 4) presence of amianthoid fibers. The combination of desmin immunoreactivity, frequently observed in MF of the breast, and amianthoid fibers, the main feature of MF of the lymph nodes, has never been observed in soft tissue MF. It is important to recognize STMF as a specific clinicopathologic entity to avoid confusion with other types of spindle cell proliferation and to differentiate it from other types of myofibromatosis.

A two-month-old infant developed a vascular tumor of the right flank which, upon biopsy, proved to be a spindle cell hemangioendothelioma. The increased capillary bed characterizing the neoplasm caused a severe thrombocytopenia together with a consumption coagulopathy (Kasabach-Merritt syndrome). The patient, who was dependent on platelet transfusions, improved quickly after interferon α-2a was given at the dosage of 3,000,000 U/m2, with resolution of the Kasabach-Merritt syndrome after three weeks and a 75% decrease of the tumor volume within three months of treatment. Med. Pediatr. Oncol. 28:358–361, 1997. © 1997 Wiley-Liss, Inc.

In neuroblastoma, high levels of mRNA for p14h trkA and p75 LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140 trkA and ME20.4 anti-p75 LNGFR mAbs. Although weak, positiveimmunostaining was found in 9 of 28 tumors for p140 trkA and in 5 of 28 tumors for p75 LNGFR . As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140 trkA (p < 0.05) and 71% (20 of 28 cases) for p75 LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.

BACKGROUND Inflammatory myofibroblastic tumor or inflammatory pseudotumor is an uncommon lesion reported in various organs and believed to be a non-neoplastic reactive inflammatory condition. The concept of benign lesion has been recently challenged from both clinical demonstration of recurrence and cytogenetic evidence of acquired clonal chromosomal abnormality. Because DNA aneuploidy can be a useful marker for neoplasia, we analyzed nuclear DNA content of these lesions using flow cytometry. METHODS In this study, inflammatory myofibroblastic tumors from nine children were examined retrospectively by evaluating clinicopathologic features and ploidy. DNA ploidy status was analyzed by flow cytometry in nuclei isolated from paraffin-embedded tumor tissues. RESULTS Three of the nine patients had local recurrence or distant metastases. Flow cytometric DNA analysis revealed five of the nine cases were diploid and four hyperdiploid (DNA indices 1.14, 1.16, 1.19, and 1.33). All lesions had a low S-phase fraction. Samples from the three subjects with clinical recurrence were all hyperdiploid. CONCLUSIONS The present data indicate that flow cytometry identifies aneuploidy (hyperdiploidy) in approximately half of the cases of inflammatory myofibroblastic tumors. This feature appears to reflect a more aggressive biologic behavior. In addition to the reported cytogenetic abnormalities, our data suggest that inflammatory myofibroblastic tumor, generally considered a benign reactive inflammatory process, may evolve as a distinct, potentially malignant, lesion. Therefore, flow cytometric DNA analysis is a suitable tool to provide the clinician with both diagnostic and prognostic information and to individuate the most feasible therapeutic approach. Cancer 1996;77:778-84.

We report on a morphologic variant of multiple myeloma, identified in a 39-year-old man, with osteolytic lesions in two ribs and three lumbar vertebrae. Serum electrophoresis was normal and immunofixation of serum and urine was negative. Histologic examination of a resected rib revealed a homogeneous population of neoplastic plasma cells with granular and eosinophilic cytoplasm. Immunohistochemical stains showed monoclonality for λ light chain and negativity for all heavy chains. At the ultrastructural level, the cytoplasm of the neoplastic plasma cells was almost totally occupied by round and elongated mitochondria, pushing the rough endoplasmic reticulum to the periphery. To the best of our knowledge, only two similar cases have been reported in the literature so far. The usefulness of obtaining a clinicopathologic correlation for the behaviour of this extremely rare variant of multiple myeloma is discussed.

We report on a 4-year-old boy with recurrent giant-cell fibroblastoma of the right nasal genal region. Histologic examination revealed that both lesions were constituted of spindle and stellate cells and a minor amount of multinucleated giant cells in a myxoid stroma containing cisternal-like spaces. Immunohistochemical examination revealed positivity for vimentin in both cellular components. Ultrastructural examination showed, in some spindle and multinucleated cells, two kinds of intracellular crystalline inclusions, located, respectively, in the cisternae of the rough endoplasmic reticulum and, apparently free, in the cytoplasm. To the best of our knowledge, this case, unusual for its location, is the first example of giant-cell fibroblastoma bearing intracellular crystalline inclusions.

A 43-year-old man underwent surgical removal of L4-L5 nerve root tumor which bulged to the extra and intradural spaces and extended as a dumbbell through the intervertebral foramen. Histological examination showed pleomorphic tumor cells with heavy melanin pigmentation. Most of the tumor cells were immunohistochemically positive for vimentin, S-100 protein and HMB-45 antigen; basic myelin protein was detectable in single tumor cells. Electron-microscopy revealed melanosomes in different stages of differentiation and some characteristics of Schwann cells, such as redundant basal lamina production. Taken together the tumor showed features of histological malignancy and incomplete schwannian differentiation with considerable overlap between melanoma and malignant melanotic schwannoma.

Background Congenital-infantile fibrosarcoma is a rare tumor of the pediatric age. It involves subjects under 5 years of age, and more than 200 cases have been reported in the literature. Methods The authors present the clinicopathologic findings of 2 cases and review the literature. Results Of our 2 patients, the first was a 2-years and 6-months-old female and the second a newborn male. The female presented a tumor in the retroperitoneum without recurrences or metastasis after 17 months, and the male on left foor with a recurrence after 3 months. Histologically, the tumors were mainly composed of spindle-shaped cells. Immunohistochemically, in both cases, neoplastic cells were positive for vimentin; focal positivity for muscular specific actin was present in the tumor of the female. Ultrastructurally, tumors were composed of mesenchymal cells with fibroblastic and myofibroblastic features. Flow cytometric analysis of the retroperitoneal tumor showed an aneuploid population of neoplastic cells. Conclusions Congenital-infantile fibrosarcoma should be considered a borderline tumor; its biologic behavior is better than that of adult fibrosarcoma. Histologic diagnosis is not easy; the microscopic picture may be confused with fibromatosis or with malignant mesenchymal neoplasms. Only a follow-up of many years can confirm the benignancy or malignancy of any individual tumor, even though clinico-pathologic features may be distinctive enough to permit its recognition.

Ten cirrhotic patients with ultrasonically discernible focal liver masses underwent fine cutting needle biopsy. Specimens were obtained from the focal lesions under ultrasound guidance and histologically diagnosed as regenerative nodules. An image analyzer was then used to determine the cytoplasmic area, nuclear area, and nuclear/cytoplasmic ratio for 100 randomly selected cells from each specimen. Data were then compared with data for specimens of normal liver tissue and data from patients with alcoholic or posthepatic cirrhosis or well-differentiated hepatocellular carcinoma (HCC). The morphometric parameters for the group of regenerative nodule specimens fell within an intermediate range between those for HCC and the nondysplastic samples, strongly suggesting a preneoplastic nature. Nine of the 10 regenerative lesions showed liver cell dysplasia, and 3 of these patients developed HCC during follow-up. Ultrasonically discernible focal masses in a cirrhotic liver should be considered preneoplastic, if not neoplastic lesions and treated aggressively to prevent their progression to outright malignancy.

We present a undescribed condition in a girl who died at 8 years of hypertrophic cardiomyopathy. Muscle and endomyocardial biopsies disclosed a selective loss of thick filaments ultrastructurally. In muscle biopsy histochemical abnormalities of myofibrillar AT-Pase were confined to type 1 fibres. Gel electrophoresis of muscle homogenate showed no qualitative abnormalities of slow and fast myosin heavy chains (MHC) and light chains, and the amount of the different myosin isozymes was in agreement with histochemical myofibrillar ATPase findings. The pathogenetic mechanisms have not been elucidated in this case but we suspect an abnormality of the beta-cardiac MHC gene, the only gene expressed in the heart and in type 1 skeletal muscle fibres.

A 58-year-old man had a biopsy taken in November 1998 and was diagnosed as having prostatic adenocarcinoma of Gleason score 5 (3+2); his serum PSA was 86.7 ng/mL. A DRE revealed a palpable nodule of increased consistency on the left lobe of the prostate; TRUS showed a hypoechoic area 1.5 cm in diameter in the peripheral zone of the left lobe of the prostate, with no evidence of capsular or seminal vesicle in®ltration. CT of the abdomen and pelvis showed no lymphadenopathy, and the bone scan and chest X-rays were normal. Laboratory tests showed a signi®cant reduction in haemoglobin (94 g/L, normal 132±170), platelet count (89 000; normal 150 000±450 000) and neutrophils (33.8%, normal 55±70). In November 1998 the patient underwent an iliac bone marrow biopsy and the histology showed tumour cell clusters; immunohistochemical staining for PSA was positive at the tumour cell sites. Histological sections from the prostate biopsy were assessed for chromogranin A expression by immunohistochemistry [1], and more than one focus with extensive staining for chromogranin A was detectable in the tumour cells (.Fig. 1). Moreover, high

One hundred forty-three biopsies of Kaposi's sarcoma (KS) from 96 patients were assessed histopathologically, and mitoses were counted. Ninety-seven samples from 66 patients were analyzed by flow cytometry. Six of 97 (5.8%) KS lesions were DNA aneuploid with a clustering around a DNA index of 1.5 (range, 1.4 to 1.6). The median percentage of S-phase plus G2-phase cells (%S + G2) was 16.7%. Increasing mitotic counts and %S + G2 were seen with progression of the phase and pattern of disease. Nodular KS and spindle cell predominant KS had the highest mitotic counts and %S + G2, with nodular KS larger than 4 mm having a higher mitotic count than those smaller than 4 mm. These findings suggest a low level of DNA aneuploidy in KS and important changes in the level of cell proliferation with the phase and pattern of the disease. However, flow cytometry does not solve the dilemma of whether KS is a hyperplastic or neoplastic process.

A careful overview of the classical appearances of Kaposi's sarcoma (KS) as well as of its variants were reviewed from the clinical and pathological point of view. The growth phases (stages) and the cellular patterns were histopathologically compared with emphasis on the developmental progression of disease as well as mitotic activity. Other morphological aspects were also assessed such as the features of the early phases and the incidence of hyaline bodies. One hundred and forty-three lesions from 96 patients mostly of the Italian sporadic type were investigated. A complete list of those entities which should be considered in differential diagnosis is shown and the dilemma of whether KS is a neoplasia or a hyperplasia is discussed.

In bladder exstrophy and to a lesser extent in epispadias the muscular tissue in the bladder wall may often be replaced by collagen. The aim of our study was to assess the relative changes of smooth muscle versus connective tissue in patients with the exstrophy-epispadias complex.Nine full thickness detrusor biopsies from children with the exstrophy-epispadias complex were analyzed. Biopsies were stained with the Masson trichrome method to differentiate muscular tissue from collagen. At x50 magnification using image software for computerized morphometry the areas of smooth muscle and collagen were measured and expressed as a percent. As controls, detrusor biopsies from 8 children with unilateral obstructive megaureter or ectopic ureter were analyzed using the same method.The average rates of smooth muscle in children with the exstrophy-epispadias complex were 7, 19.3 and 31.5%, respectively, in newborns, and before and after bladder neck reconstruction. In controls the rate averaged 56.5%.The ratio of smooth muscle-to-connective tissue increases from the newborn period to puberty in the exstrophy-epispadias complex. After staged reconstruction is completed this ratio remains below normal, although it is increased. Such a change may represent a histological marker of the inadequate volume increase of some of these bladders.

Desmoplastic small round cell tumor (DSRCT) is a neoplasia that occurs mainly in childhood and involves abdominal or peritoneal sites, coexpressing ectodermal and mesenchimal immunophenotypic markers, and is endowed with an impressive stromal desmoplasia that tends to decrease on tumor relapse. To date, over 150 cases have been collected in the literature. Its presumed neuroectodermal histogenesis has been challenged by cytogenetic findings different from those usually associated with neoplasms of neuroectodermal origin. The authors report a case bearing clinical and histologic aspects of typical desmoplastic retroperitoneal small cell tumor, with intense and diffuse nuclear immunopositivity for WT1, but lacking divergent immunophenotype. Ultrastructural investigation revealed that desmoplasia could result from fibrillary synthesis by neoplastic cells.

We describe here the clinicopathological findings in a child with congenital nephrotic syndrome (CNS) non-responsive to medical therapy who developed acquired cystic kidney disease (ACKD) in both native kidneys after long-term peritoneal dialysis. This case indicates that CNS is a further pathologic condition related to the development of ACKD.

Treatment of nephroblastoma (Wilms' tumor) has presently achieved a 90% survival rate. Stage and grade are considered the most reliable prognostic parameters, but other biological factors are under study in order to improve patient stratification. Deoxyribonucleic acid (DNA) ploidy has been suggested to be useful in this setting. We retrospectively studied 79 patient with nephroblastoma (58 pretreated with chemotherapy and 21 not pretreated) by means of flow cytometry. DNA content and synthetic phase values were correlated with pathologic features and outcome. DNA modifications induced by chemotherapy were investigated. Sixty-nine tumors were diploid and 10 aneuploid. DNA content did not correlate with clinical course and was not modified by pretreatment. Aneuploid tumors were restricted to lower stages. Mean S-phase rate was lower and did not vary according to histology in pretreated tumors, while it was higher and increased with grade (p = 0.007) in previously untreated tumors. The fraction of cells in synthetic activity was related to outcome: Patients whose tumors displayed higher S-phase rates had a more favorable clinical course. Ploidy did not appear to be of prognostic significance. S-phase rate decreased after chemotherapy (p = 0.0002) and was related to survival. The worse outcome of pretreated patients might be attributed to a minor sensitivity to postoperative treatment: Preoperative chemotherapy would decrease the cell proliferation and might select resistant cellular clones of (possible) neoplastic residues.

The case of a 61-year-old woman with Whipple's disease-associated sicca complex is reported. Tropheryma whipplei infection was diagnosed by histological and ultrastructural examination of the jejunal mucosa and sequence analysis of the bacterial 16S ribosomal DNA. The role of vitamin A malabsorption in sicca complex secondary to Whipple's disease is discussed.

The term "neuronal ceroid lipofuscinosis" (NCL) describes a complex of inherited neurodegenerative conditions associated with storage of lipopigments in brain tissue. In 1989 Dyken proposed a classification of NCL based on the age, clinical symptoms, and ultrastructural aspects of the lipopigments. At the ultrastructural level it is possible to distinguish 5 different patterns of osmiophilic lipopigments: usual lipofuscin, fingerprint deposits, granular profiles, curvilinear bodies, and microtubular aggregates. The concept that each ultrastructural pattern was the counterpart of a specific clinical type has been proved not to be true. Advances in molecular genetic techniques have allowed the identification of defective genes and their protein products in several NCL clinical forms. Ceroid lipofuscin deposits may be ultrastructurally observed not only in neuronal cells, but also in several other sites, such as trophoblastic cells, thus permitting prenatal diagnosis. In spite of recent advances in immunohistochemical identification of biochemical markers, the ultrastructural identification of lipofuscinic pigments remains the gold standard to identify NCL, together with clinical aspects and respective gene defects. This study describes the ultrastructural aspects observed in 8 cases of NCL syndromes (3 juvenile, 3 infantile, 1 late infantile, and 1 congenital clinical form). In these patients, genetic analysis was also performed.

Summary Myofibroblasts are spindle cells having ultrastructural features in common with smooth muscle cells and fibroblasts. In the last few years, tumours have been described in which myofibroblasts represent not only a reactive mechanism but also a true neoplastic component. They constitute new nosologic entities which might be termed “myofibroblastic tumours”. Tumours with benign and, rarely, malignant behaviour are reported to belong to this group of lesions. Recently, a third tumour type with borderline biological course, named “inflammatory myofibroblastic tumour” (IMT), has been identified, a condition that has been regarded as a benign and reactive disorder for a long time. Only in recent reports has been demonstrated that, in spite of an apparently benign morphological pattern, some cases of IMT have a malignant course. In this connection, DNA analysis by flow cytometry is a valuable diagnostic tool, because it allows identification of the ploidy status, a procedure that is often useful for predicting the nature and the biological behaviour of the lesion. In this study, 11 cases of myofibroblastic tumours were examined retrospectively by evaluating clinicopathological features and DNA ploidy status by flow cytometry. The diagnosis of myofibroblastic tumour was confirmed by performing histology, immunohistochemistry, and electron microscopy in all patients. In detail, these 11 cases were composed of 1 benign myofibroblastoma, 1 myofibrosarcoma and 9 IMTs. Among these myofibroblastic tumours, all those with local recurrence or distant metastases (one myofibrosarcoma and three IMT) showed an aneuploid cell population demonstrable by flow cytometric analysis, whereas the other cases with benign course (one benign myofibroblastoma and six IMT) exhibited an euploid DNA content. These data suggest the following: a) Besides the rare myofibroblastomas and myofibrosarcomas, IMTs represent a larger group of lesions with potentially different biological and clinical course. b) DNA flow cytometric analysis is a reliable tool that supports histopathological examination in characterizing those cases of IMT that, though being malignant, mimic benign lesions. Consequently, it establishes the basis for a different therapeutic approach according to the euploid or aneuploid DNA content.

A girl affected by a restrictive cardiomyopathy with neuromuscular involvement is described. Morphological examination showed a pattern of multicore myopathy and with electron microscopy a sarcoplasmic accumulation of electron dense granular and filamentous material was demonstrated both in skeletal muscle and heart. This peculiar electron dense material corresponded to increased desmin in muscle and cardiac fibres and was demonstrated immunohistochemically.

Objective To determine the accuracy of comparative cytologic and frozen section intraoperative diagnosis in neuropathology and the relevance of diagnostic accuracy during both craniotomic and stereotactic biopsies and to provide further data on rare and/or diagnostically controversial lesions. Study design Both cytologic and frozen section preparations were employed in the intraoperative diagnosis of 85 consecutive central and peripheral nervous system lesions obtained from classical surgery (70 samples, 4 of which were intramedullary) and stereotactic biopsies (15 samples). Results Combining cytologic and frozen section details allowed a fair diagnosis in 81 cases (95.29%), confirmed on paraffin sections. In the remaining cases intraoperative misdiagnosis was due to technical-staining defects (1 case); absence of tumor differentiation, resolved only by ultrastructural examination (2 cases); and marked tumor heterogeneity, resolved by wide tissue sampling and immunohistochemistry (1 case). Conclusion Besides providing a general description of cytologic and frozen section criteria useful in intraoperative diagnostic neuropathology and adding further details about some problematic and/or rare entities, our work confirmed: (1) the usefulness of comparative cytologic and frozen section examination in the intraoperative diagnosis of central nervous system lesions, (2) the relevance of the accuracy of intraoperative diagnosis during both craniotomy and stereotaxis, including intramedullary samples; and (3) the importance of fair "conduct" in intraoperative neuropathology, always comparatively considering morphologic and clinicoradiologic data.

In order to directly ascertain the presence of HCV virus infection in livers of patients with HCV chronic hepatitis, we investigated, by transmission electron microscopy (TEM), liver biopsies from 2 adults and 4 children for the presence of virus-like particles (VLPs). The plasmas of these HCV-positive patients were HCV-RNA-positive, with high ALT values. In liver tissue samples examined, we were able to detect plus and minus strands of HCV RNA by strand-specific RT-PCR. Aggregates or single VLPs of about 45 nm in diameter were detectable in variable amounts in endoplasmic cisternae and in hepatocyte cytoplasms of infected patients. These results emphasize the relevance of performing TEM assays to confirm the diagnosis of HCV infection.

Few published reports describe patients with giant cell fibroblastoma, a rare, benign soft-tissue tumor that recurs locally and predominantly arises in children. A 4-year-old boy underwent surgery for removal of a giant cell fibroblastoma in the paranasal region, an unusual site. Six months after excision the tumor recurred locally. Immunohistochemical examination of the primary tumor and recurrence revealed vimentin positive staining in the cytoplasm of all the cells. The multinucleated giant cells and the flat cells bordering the vessel-like spaces were negative for Factor VIII-related antigen, S-100 protein, actin and desmin. Some histiocytes stained positively for alpha-1-antitrypsin, alpha-1-antichymotrypsin, antimacrophage and lysozyme antibodies. These immunoreactions indicate that giant cell fibroblastomas have a fibrohistiocytic origin.

Bacillary epithelioid angiomatosis (BEA) is a rare cutaneous disorder usually affecting patients with human immunodeficiency virus (HIV) infection often misdiagnosed as a vascular tumour. We describe a 51-year-old, HIV-positive, Caucasian, homosexual male who developed scattered papulo-nodular lesions with clinicopathological and ultrastructural features of BEA. He had a dramatic therapeutic response to systemic antibiotics. There has been a lack of such reports in the European literature. The differential diagnosis is discussed and a brief review of the English literature to date is included.

The clinical, morphological and biochemical findings of a sporadic case, showing accumulation of desmin-type intermediate filaments in skeletal muscle and myocardium are described. Desmin storage was demonstrated by immunofluorescence, sodium dodecyl sulfate gel electrophoresis and two-dimensional gel electrophoresis. These findings are in agreement with those of Rappaport et al. (FEBS Lett. 231:421–425, 1989). A sensory-motor polyneuropathy was established by electrophysiological studies and, ultrastructurally, intramuscular nerves showed accumulation of neurofilaments and neurotubules with formation of axonal spheroids. These findings are discussed considering all previous reports with related conditions.

The 4th case of plasma cell neoplasm associated with a hypereosinophilic syndrome is described and compared with the previous reports. Hypereosinophilia in the present patient displayed some borderline traits with eosinophilic leukemia. Myeloproliferative disorders of the eosinophilic line often present as a precancerous state, but sometimes they seem to acquire malignant independence. In our patient the occurrence of a plasmocytoma with a dramatic course leads to suspect an underlying complex genetic aberration.

Summary 30 patients in paediatric age have been submitted to endocardial biopsy of the right ventricle, most of them affected by a dilated cardiomyopathy. Our aim was to improve knowledge on this disease using ultrastructural morphometric analysis. An enlargement of myocardial cells with granular aspects of the cytoplasm, known as cloudy swelling, was observed at histological level. Electronmicroscopy showed two main abnormalities: 1) a constant increase of the chondrioma resulting in nuclear deformation and myofibrillary dislocation towards the sarcolemma. 2) disarrangement of thin (actin) and thick (myosin) myofilaments. Such myofibrillary dislocation, designated as fibrillar segregation, suggests how mycardial fibres may loose their ability to contract. The stereological study of these two ultrastructural abnormalities showed that mitochondria are increased in number and size and that the loss of contractile properties of myocardial cells can be related to myofibrillar segregation.

Pairs of rats were immunized with keyhole limpet hemocyanin (KLH) and simultaneously labeled with thymidine-methyl-3H or 5-iodo-2'-deoxyuridine-125I. From 10–50 days later, their lymphoid organs were examined 3 days after anamnestic stimulation with KLH or after primary injection of BGG. Light and electron microscopic study of the labeled cells revealed that immunologic memory resided in the mature resting monoribosomal lymphocyte which, upon stimulation, transformed to an immature polyribosomal lymphocyte and mitotically active blast cell. These latter elements differentiated into plasma cells directly or after mitosis.

Chronic renal failure due to lymphomatous infiltration is rare. We report a case of end-stage renal failure due to bilateral massive lymphomatous infiltration confined to the kidneys and pancreas. Renal insufficiency was due to interstitial fibrosis and striking tubular atrophy.

A case of primary Kaposi's sarcoma of the lymph node (single node involvement) is reported on here. It occurred in a white, Italian boy 10 years of age. An extensive review of the literature showed that this was only the second childhood case of the disease among non-acquired immune deficiency syndrome (AIDS)-related people of the Western world.

Various pathological disorders have been associated with primary aldosteronism, including glucagonoma, phaeochromocytoma and primary hyperparathyroidism. In this report, a case of adrenal myelolipoma (a rare non-functioning tumour composed of mature adipose tissue and normal haematopoietic elements similar to bone marrow cells), aldosterone-producing adenoma and a pituitary microadenoma coexisting in a 62-year-old man with a 15-year history of arterial hypertension, previous ablation of an autonomously-functioning thyroid adenoma, multiple lipomas and an heterozygosity of the retinoblastoma (RB) susceptibility gene is reported. We believe that this case probably represents another variant of the multiple neoplasia syndrome and we speculate that structural alteration of the RB gene may play a role in the tumorogenesis.

A case of ossifying fasciitis in a 22-year-old woman is described. The lesion, which appeared suddenly, was located on the tip of the nose. Histologically the lesion contained spindle-shaped myofibroblastic cells, trabeculae of woven bone rimmed by plump osteoblasts within a myxoid stroma.

A muscle biopsy and autopsy study of a child who died at 14 months of respiratory failure is described. A diagnosis of infantile cytoplasmic body myopathy was made due to the high percentage of cytoplasmic bodies (CBs), particularly in respiratory muscles. No pathological abnormalities were found in the central nervous system, peripheral nerves or visceral organs. Immunohistochemical studies suggested that the central core of CBs was stained for fibrillary actin, being surrounded by a positive signal for desmin. A differential diagnosis as to other conditions involving proliferation of CBs is discussed.