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Das RET-Proto-Onkogen ist das zentrale fur die Entstehung eines M. Hirschsprung verantwortliche Gen, wobei RET-Mutationen auch bei anderen pathologischen Lasionen vorkommen. Bei Hirschsprung-Patienten konnten eine Reihe verschiedener RET-Mutationen festgestellt werden. Besondere Aufmerksamkeit sollte denjenigen Patienten gewidmet werden, die Mutationen der Exone fur die entscheidenden Zysteinreste aufweisen, welche fur MEN2A pradisponieren. Bei diesen Patienten kann der M. Hirschsprung selten mit der Entwicklung neuroendokriner Tumoren, wie mit einem medullaren Schilddrusenkarzinom oder einer MEN2A assoziiert sein. Daher ist eine prophylaktische Thyreoidektomie dann ratsam, wenn eine tumorassoziierte RET-Mutation gefunden wurde. In MEN2A/Hirschsprung-Familien konnen die RET-Mutationsanalyse, Tumor-Screening und ggf. eine prohylaktische Thyreoidektomie wie bei MEN2A empfohlen werden. Der multigenetische Ursprung des M. Hirschsprung in Abwesenheit einer spezifischen „Standard-Hirschsprung-Mutation“ macht eine genetische Routinediagnostik unmoglich.

HAEMATOLOGICA N.RO 7

The proto-oncogene RET is the major gene responsible for Hirschsprung's disease (HSCR), with RET mutations also implied in different pathologies. A variety of mutations of the RET proto-oncogene have been detected in HSCR patients. Special attention should be paid to rare patients who carry mutations of one of the critical cysteine residues of these exons, known to predispose to MEN2A. In these cases, HSCR can be associated with the development of neuroendocrine tumors such as medullary thyroid carcinoma (MTC) or MEN2A, for which a prophylactic thyroidectomy is advisable in the presence of a tumor causing RET mutation. In combined MEN2A/HSCR families, RET gene testing, tumor screening and prophylactic thyroidectomy are indicated as in MEN2A. The multigenic origin of HSCR and the absence of a "standard" RET mutation associated with HSCR currently make a routine molecular diagnosis impossible.

Gastric lymphomas have been the subject of intensive studies in the last years and important progress has been made regarding their etiopathogenesis and therapy. Diagnosis of gastric lymphoma is usually made on bioptic material taken at endoscopy. Histopathologic diagnosis is frequently difficult. This paper summarizes the main diagnostic criteria of this setting. It analyses the morphological, immunohistochemical and molecular features to be considered for the differential diagnosis between: reactive process vs low grade B-cell gastric MALT lymphoma, B-cell MALT lymphoma vs other low grade lymphomas involving the stomach and low grade vs high grade gastric lymphoma. The histopathological aspects of gastric biopsies after antibiotic treatment for Helicobacter pylori eradication and the role of molecular analysis in the follow-up of these patients are also considered.

The lymphohistiocytic (LH) variant of anaplastic large cell lymphoma (ALCL) has, for a long time, been considered typical of children and adolescents. The aim of this study is a detailed characterization of a case of this peculiar ALCL subtype affecting an adult patient.A 36-year old male presented with diffuse adenopathy and systemic symptoms (high fever, anorexia, asthenia); a diagnosis of CD30+/ALK+ ALCL, LH variant, was morphologically suspected and corroborated by immunohistochemistry that was crucial for the definitive diagnosis and subtyping.The neoplastic population consisted of cells highly variable in size and shape but more often isolated and largely obscured by a predominant reactive cellular infiltrate of histiocytes and plasma cells. The lymphoma cells exhibited a null non-B non-T antigenic profile, but reacted strongly for the Ber-H2/CD30, EMA, ALKc anti-TIA-1 monoclonal antibodies. The patient underwent chemotherapy plus bone marrow transplantation and, one year after diagnosis, he is well and in complete remission.Our findings provide additional evidence that: a) ALK+ lymphoma represents a single disease with a broad spectrum of morphology; b) clinicians and pathologists should be aware of the possible occurrence of LH variant of ALK+ ALCL also in adults in whom a favorable response to therapy may be expected despite systemic disease and an aggressive clinical presentation.

We report the case of a 42-year-old man who presented with B-symptoms, moderate splenomegaly and multiple nodules in the liver. Histologically, lymphocytic infiltrates were seen in the portal spaces and sinusoids of the liver and in the paratrabecular areas of the bone marrow. After excision, the spleen showed minimal disturbance of architecture with an expansion of the follicular marginal zones. These findings were considered inconclusive for lymphoma and the patient was treated only with non-steroidal anti-inflammatory drugs for persisting fever. Five months after splenectomy, a bone marrow biopsy still showed diffuse lymphoid infiltrates. From then on, the patient's condition improved with no further evidence of disease. Ten years after splenectomy the case was reconsidered as a splenic marginal cell lymphoma, indolent variant. Immunohistochemical and gene rearrangement studies demonstrated the monoclonality of the splenic proliferation, supporting the diagnosis. A further bone marrow biopsy did not detect residual lymphoid infiltrates. This case confirms that splenic marginal zone cell lymphoma may have a deceptively favorable course, even when presenting at an advanced stage. Moreover, it indicates that extrasplenic localizations of the lymphoma may persist for a long while after splenectomy but may vanish over time without therapy.

The authors report a single case of primary soft tissue CD30+ non anaplastic non-Hodgkin's lymphoma. The clinical, histological and immunohistochemical features of this peculiar lymphoma type are discussed. Within extranodal lymphomas, a primary soft tissue involvement is rare and the literature lacks exhaustive data on the clinical behaviour of these malignancies. In our case, the prognosis appeared more closely related to the clinical stage of the disease than to histology.

Bone marrow abnormalities may be found in patients with cancers even without marrow metastases. We have seen that patients with non-hematologic neoplasias may show bone remodelling, stromal modifications, reactive changes and myelodysplastic alterations of erythro-, granulo- and megakaryocytic series comparable to those found in myelodysplastic syndromes (MDSs).At the beginning of the study 58 bone marrow biopsies (BMBs), performed in 40 patients with previously diagnosed cancer from different primary sites but without marrow metastasis (group A), were evaluated. Osseous and stromal modifications, marked reactive changes, quantitative and qualitative alterations of erythro-, granulo- and megakaryopoiesis were observed. Afterwards, 30 BMBs from 20 patients without a previous diagnosis of neoplasia (group B) were found to have features similar to those discovered in group A. Further investigations detected malignant tumors in all these cases. The findings of the two groups were compared with our former observations on myelodysplastic syndromes. The main differences between groups A-B and MDSs regarded bone remodelling, stromal modifications and reactive changes.These marrow alterations linked to a neoplasia may be considered paraneoplastic. They may cause problems for a differential diagnosis with some proliferative diseases and, above all, with primary MDSs. The reported features should prompt the pathologist to suggest a search for possible occult cancer.

A theoretical analysis was carried out in order to study the influence of the thermal inertia of building struc tures on thermal comfort and energy consumption.

Maximum limit of vapor concentration of the inside air that does not create mould growth and condensation on the surface of exterior walls has been analyzed in non-steady state conditions. The calculations have been carried out for three different exterior walls and various air changes. Results show that both thermal storage capacity of the walls and of the inter nal structures affect the level of the permissible vapour concentration inside the dwelling.

An experimental investigation was conducted under conditions of saturated pool boiling of water at atmospheric pressure on thin, horizontal, cylindrical walls of different metals and thicknesses, electrically heated. The heating walls, ranging in thickness from 5 to 250 μm, were obtained by plating copper, silver, zinc, nickel, and tin on nonmetallic rods. Experiments showed that the heat transfer coefficient can be affected, in particular conditions, by the heating wall thickness. In particular, it resulted that the smaller the thermal conductivity of the metal layer, the higher the influence of the thickness. A semiempirical correlation of the form ΔT = (q/A)nf(κd, √κρc) suitable to correlate the experimental data within ±15 percent in the whole range of variables here investigated is proposed.

SUMMARYClinical and chromosomal studies of a case of gonadal dysgenesis. The patient presented primary amenorrhea, rudimentary uterus, ipoplastic tubes and gonadad streak. No Barr bodies or drumsticks were found, and the chromosome analysis revealed a mosaic of the type XO/X + centric fragment. The pertinent literature is reviewed, and attention is drawn to the possible existence of a secretion of the steroid type in the Leydig-like cells present in the gonadal streak.

IgA nephropathy of 5-years’ duration in a 14-year-old boy evolved into diffuse crescentic glomerulonephritis with rapid progression to terminal renal failure. This report suggests that in rare cases I

The cytoplasm of cultured skin fibroblasts derived from four unrelated and from three related patients with myotonic muscular dystrophy exhibits high amounts of metachromatic granular material and of alcianophilic material with Alcian blue containing 0.1 M MgCl2. Alcianophilia disappears when the staining solution contains 0.3 M MgCl2, i.e. is probably due only to carboxyl group of glycosaminoglycans.

After a clinical and histo-pathological introduction, the paper presents a case of Piostomatitis Vegetans, a rare stomatitis coexisting with chronic inflammatory disease of the intestinal tract, that was treated with local corticosteroids.

A 4-year-old boy with recurrent infections and his clinically healthy father showed a severe, isolated defect in bactericidal activity of peripheral neutrophil leukocytes (the mother and the only sister were normal). Lymph nodes, spleen and liver of the child presented a massive infiltration by macrophages. Such infiltration and the segmentary albinism of the hair resemble traits of the Chediak-Higashi syndrome, but some of the most relevant traits of this syndrome are absent, since all other neutrophil functions were normal in our patient.

A case of large cell lymphoma presenting with hemophagocytic syndrome is reported. The clinicopathological findings suggested a diagnosis of malignant histiocytosis, but on the basis of immunohistological studies Ki-l lymphoma was diagnosed. Neoplastic cells expressed activation antigens such as HLA-DR, IL 2R, T10 and Ki-l, and showed high proliferative activity, but were devoid of T and B cell markers. The high percentage of reactive macrophages found in the bone marrow and lymph node probably reflected the release of lymphokines by the tumor population. The patient was treated with aggressive chemotherapy and is in complete remission at 8 months from diagnosis.

Adriamycin cardiotoxicity was morphologically evaluated in mice treated iv ten times at three dose levels which were equal to fixed fractions of the LD50. Good correlation between the degenerative heart lesions, scored according to a nonparametric scoring system, and the doses was found and allowed calculation of a median cumulative cardiotoxic dose of 36.4 mg/kg of body weight (121.5 mg/m2). The method is suitable for quantitative screening of the potential cardiotoxicity of new anthracycline analogs under standardized conditions.

A 20 year old man with beta thalassaemia developed symptoms of the sicca syndrome. His serum contained rheumatoid factor and antinuclear antibodies. A biopsy specimen of labial salivary gland showed large accumulations of haemosiderin within the parenchymal cells of the acini. Although in this case the sicca syndrome could not be definitely distinguished from Sjogren's syndrome, the patient's HLA type was not the one usually associated with Sjogren's syndrome. Histological appearances suggested that the causative factor of the sicca syndrome was iron overload owing to an intensive blood transfusion regimen.