Hypopituitarism and antiphospholipid syndrome.

Vascular damage is a well known cause of hypopituitarism since Sheehan's report of postpartum pituitary necrosis; it has subsequently been reported that also sickle-cell anemia, eclampsia, pituitary apoplexy and other pathologies may induce failure of the anterior hypophysis through this mechanism. The antiphospholipid syndrome (APS) is characterized by widespread arterial and venous thrombosis with resulting different clinical features; Addison's disease due to adrenal thrombosis is the only endocrine involvement reported so far in this syndrome. We report here a case of global anterior pituitary insufficiency which developed soon after cerebral ischaemic stroke in a 62 year aged woman with Lupus aicoagulant activity (LAC) and large atrial thrombosis; underlying pathologies were excluded by appropriate investigations. Therefore in our opinion this is the first case in which anterior hypopituitarism is reported in the clinical constellation of APS and the second type of endocline involvement.

[Meningeal carcinosis: early clinical manifestations of inflammatory cancer of the breast]. / Carcinosi meningea: manifestazione clinica precoce di cancro infiammatorio della mammella.

Inflammatory carcinoma of the breast accounts for only 1-6% of mammary cancer in Caucasian women and is characterized by a poor prognosis; distant metastases frequently appear in fact in an early stage of disease and moreover metastatic spreading follows unpredictable ways. In this study we report on a case of a female patient in whom persistent signs of increased intracranial pressure, following the diagnosis of inflammatory carcinoma of the breast, have been referable to the tumour seeding the meninges in the absence of systemic disease. This peculiar and unusual form of neoplasia is up today a challenge for the clinician, both because of therapeutic difficulty and of unexpected metastases which, in turn, worsen the prognosis. Particularly, in our opinion, meningeal localization must be suspected even in the absence of distant metastases.

Trilineage response to granulocyte colony-stimulating factor administration in a patient with myelodysplastic syndrome.

We report a 72-year-old man with refractory anemia with excess of blasts who presented severe pancytopenia and pneumonia and received granulocyte colony-stimulating factor (G-CSF) treatment over a 6-week period. In addition to a dramatic increase in mature neutrophils, platelet count and hemoglobin level, the patient achieved a hematological remission which continued for more than 5 months despite discontinuation of the treatment. This observation confirms that in some cases during G-CSF treatment erythropoiesis and thrombopoiesis may improve in addition to the expected effect on neutrophils. While the patient remained in hematological remission, bone marrow examination revealed trilineage dysplasia. This finding suggests that the hematological remission in this patient may not have resulted from a recovery of non-clonal hematopoiesis of a normal clone, but may have derived instead from the monoclonal hematopoiesis of a neoplastic clone.

Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial.

We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.

Establishment and characterization of a B-cell line derived from a patient with a myelodysplastic syndrome which expresses myelomonocytic and lymphoid markers.

We describe a novel continuous B-cell line (PV-90) derived from a patient with myelodysplastic syndrome (MDS) and originating from spontaneous infection with the Epstein-Barr virus (EBV). The patient progressed to acute myeloblastic leukaemia (AML) 5 months after clinical onset of MDS. PV-90 is of clonal origin as indicated by the presence of immunoglobulin (Ig) gene rearrangements, monoclonal surface immunoglobulins, and a single DNA restriction fragment corresponding to the EBV genomic termini. PV-90 cells also express a number of myelomonocytic markers, including alpha-naphthyl acetate esterase (ANAE), coagulation factor XIII, and CD68 antigen. Moreover, PV-90 cells constitutively express the c-fms proto-oncogene mRNA as the patient's blast cells did. Whereas a trisomy 11 (+11) was found in the patient's bone marrow cells, PV-90 cells had a normal karyotype initially, but at 4 months showed two different and independent chromosomal abnormalities: 90, XX, -Y, -Y, t(9;16) (q11;p13), and 90, XX, -Y, -Y, t(17;18) (p13;q21), the latter possibly involving the p53 (17,p13) and bcl-2 (18, q21) proto-oncogenes. The early development of these chromosomal aberrations is consistent with a genetic instability of PV-90 cells. Expression of bi-lineage markers and genetic instability may suggest that PV-90 cells originated from transformation of a myelodysplastic progenitor cell capable of both myeloid and B-cell differentiation. The PV-90 cell line might be useful in a number of studies, including the possible role of c-fms in cell differentiation, pathogenetic mechanisms of human preleukaemia and lineage promiscuity in acute leukaemia.

[Is hypereosinophilic syndrome a potentially malignant condition?]. / E la sindrome ipereosinofila una condizione potenzialmente maligna?

The existence of eosinophilic leukemia (EL) has been controversial since it was first described. Recently, some authors have suggested that EL is part of a spectrum of eosinophilic diseases termed hypereosinophilic syndrome (HS). EL diagnosis is very difficult, especially if abnormal chromosome are not present, because HS comprises multiple disease entities of unclear etiology with the common features of prolonged eosinophilia of undetectable cause and organ system dysfunction. We present a case of HS whose findings are consistent with a leukemic process. For two years the patient showed only sharp hypereosinophilia; his clinical course was then marked by signs and symptoms of granulocytic sarcoma (GS), an extramedullary tumor composed of granulocytic precursor cells. GS as a complication of EL was described and in some cases the diagnosis of leukemia was made only on the basis of the GS complication. The formation of eosinophilic GS also suggests a diagnosis of LE in our case of HS. Finally, we always consider HS as a potential malignant disease.

[Cutaneous extramedullary hematopoiesis in idiopathic myelofibrosis. Description of a case]. / Ematopoiesi extramidollare cutanea in mielofibrosi idiopatica. Descrizione di un caso.

The Authors present a case of cutaneous extramedullary hematopoiesis in a 63-year-old male patient with agnogenic myeloid metaplasia. The skin lesions appeared before splenectomy as multiple papules and nodules on the trunk. Histologic examination of a lesion showed all the tree components of the hematopoietic tissue, i.e. myeloid, erythroid and megakaryocytic series. A review of the literature revealed 18 previously reported cases, with polymorphous clinical manifestations of skin involvement. The possibility of extramedullary hematopoiesis should be considered in a patient with agnogenic myeloid metaplasia who shows cutaneous eruptions.

[Idiopathic hepatosplenic granulomatosis]. / Granulomatosi epatosplenica idiopatica.

Granulomas in the liver are identified in 3-10% of all liver biopsies. Although granulomas frequently represent a sign of either infectious or non infectious disease, 20% of the hepatic granulomas lack an identifiable etiology. These cases are defined as idiopathic granulomatous hepatitides (IG). We describe four cases of disease resembling a lymphoid malignance in which IG could be diagnosed by laboratory, radiological (XR, CT), ultrasonographic, histological and follow-up studies of the patients. We suggest that IG may be suspected in patients with granulomas in the liver, self-limited fever of unknown origin, low epatosplenomegaly, eosinophilia less than 5%, in the absence of infectious, lymphoid or sarcoid diseases. We recommend laparascopy as an important diagnostic tool.

Meningeal leukemia following lymphoid blast crisis in chronic myeloid leukemia: therapeutic implications.

Five of 40 patients with chronic myeloid leukemia (CML) had lymphoid blast crisis and 4 of them achieved complete remission of metamorphosis with vincristine and prednisone. While in hematologic remission, two of these subjects developed meningeal leukemia. Clinical and biologic data indicated that the course of the disease after lymphoid blast crisis was very similar to that of acute lymphoblastic leukemia (ALL). It is suggested that patients with CML who develop lymphoid blast crisis should be treated with an intensive therapeutic protocol including early prevention of meningeal leukemia.