Flare and tumor lysis syndrome with atypical features after letrozole therapy in advanced breast cancer. A case report.

Tumor lysis syndrome, which develops after effective therapy of malignant conditions and leads to hyperuricemia, hyperkaliemia, hyperphosphatemia, hypocalcemia and elevated lactate dehydrogenase, is uncommon in solid tumors. In breast carcinoma it can be associated with tamoxifen flare, i.e. a transient increase in symptoms, mainly bone pain, observed shortly after the start of tamoxifen therapy. We report the case of a patient with advanced breast carcinoma involving the pleural space, unresponsive to combined chemotherapy, who experienced rapid worsening after the initiation of letrozole. Her symptoms included shock, bilateral pleural effusion, cardiac tamponade and oliguria. Laboratory parameters disclosed elevated transaminase, lactate dehydrogenase, uric acid and D-dimer blood levels. The patient was in critical condition for nearly 2 weeks. She improved progressively and has remained well and in complete remission for 20 months. This clinical picture suggests increased damage to the pleura (and probably the pericardium) and rapid leakage of tumor products, following the start of endocrine therapy. Letrozole is a non-steroidal aromatase inhibitor which is used in advanced breast cancer, resistant to first-line endocrine/chemotherapeutic treatment. Our review of the literature did not disclose any other descriptions of flare and tumor lysis syndrome after aromatase inhibitor therapy. Moreover, this case was characterized by atypical and complex clinical features. The aim of this presentation is to point out the practical significance, in neoplastic patients, of the differential diagnosis between symptoms due to tumor progression and those associated with anomalous reactions to therapy.

[Lipid metabolic disorders in obesity: their epidemiology, physiopathology and clinico-therapeutic implications]. / Le turbe del metabolismo lipidico nell'obesità: epidemiologia, fisiopatologia ed implicazioni clinico-terapeutiche.

The centralization of body fat, particularly in abdominal or visceral depots, is associated with qualitative and quantitative lipid abnormalities. Examples of these qualitative alterations include changes in low density lipoprotein composition, namely an increased number of small or dense low density lipoprotein particles, which seem to be prone to increased lipid oxidation. Oxidative modification of low density lipoproteins is involved in atherosclerotic development of the arterial wall. Alterations of lipid composition often arise in a context of insulin resistance with hyperinsulinism. Genetic features, such as apolipoprotein E polymorphism, also play a significant role in lipoprotein metabolism. The principle treatment of obesity and associated dyslipidemia is to reduce energy intake through diet. Moderate exercise is effective, especially in patients with insulin resistance. Drug therapy is considered primarily for patients who refuse to make behavioral changes.

Portal and mesenteric thrombosis in protein S (pS) deficiency.

Portal and/or mesenteric thrombosis is a rare occurrence, and often an underlying hypercoagulable state can be found. We describe a case in which a mesenteric infarction due to mesenteric venous thrombosis occurred as the first manifestation of an inherited type I deficiency of protein S, whereas signs of portal thrombosis emerged later.

A laboratory and thrombokinetic study of HCV-associated thrombocytopenia: a direct role of HCV in bone marrow exhaustion?

OBJECTIVE: In order to investigate HCV associated thrombocytopenia, 6 patients suffering from this disease, in the absence of splenomegaly and other common causes of peripheral platelet destruction, underwent laboratory and scintigraphic tests. RESULTS: Thrombokinetic studies revealed a significant, nearly linear, delayed splenic accumulation with normal or low-normal values for the average platelet life span, low-normal recovery, and depressed platelet production. Megakariopoiesis was normal or slightly increased. HCV infection of the megakariocytes was found in two patients. Autoantibodies and liver disease were also investigated. CONCLUSIONS: A role of immunological mechanisms in HCV associated thrombocytopenia appears to be ruled out. The authors conclude that tests for HCV infection should be included in the evaluation of thrombocytopenia in adults and a possible direct involvement of HCV cannot be excluded.

Lymphoproliferation in type II mixed cryoglobulinemia.

OBJECTIVE: The role of the hepatitis C virus (HCV) in the etiology of type II mixed cryoglobulinemia (MC) has been well established, but the pathogenetical relationships among the virus, the immune system, the natural history of MC, and lymphoproliferation in the bone marrow and liver need to be further elucidated. METHODS: Eighty-two patients with HCV positive type II MC and 20 subjects with chronic hepatitis C without MC were studied: bone marrow and liver specimens were examined by routine histology and immunohistochemistry, particularly focusing on parameters related to disease behaviour, such as the expression of the bcl-2 oncogene product and the proliferation-associated Ki67 antigen. RESULTS: In most MC patients there were lymphoid infiltrates within the bone marrow showing a monomorphic cytology, frequent immunoglobulin light chain monotypic restriction, expression of the anti-apoptotic bcl-2 oncogene product, and a low proliferative capacity (Ki-67 < 3%). On the other hand, in all non-cryoglobulinemic patients a bone marrow picture of reactive lymphoplasmacytosis was found. In both MC and chronic hepatitis patients, the liver biopsy showed portal infiltrates consisting of T-cells, associated with a significant B-cell component; the latter was particularly abundant in MC, where it was frequently arranged in pseudo-follicles. The B-cell component expressed the bcl-2 oncogene product and CD5 antigen, thus suggesting that the immune system is actively involved in the production of liver damage both in MC and non-cryoglobulinemic patients. It is worth noting that in MC patients (but not in the non-cryoglobulinemic patients) these CD5+/bcl-2+ B-cells frequently also exhibited a monotypic restriction bearing an IgM kappa. CONCLUSION: Our findings in these liver and bone marrow studies further support the role of a lymphoproliferative disorder in the pathology of type II MC: the B cells involved accumulate due to the inhibition of apoptosis, and their low proliferative index justifies the indolent course of the disease. HCV probably interacts with these B-cells, facilitating their clonal expansion.

Parenchymal renal involvement in three cases of non-Hodgkin lymphomas: clinical and pathological features.

Parenchymal neoplastic invasion of the kidneys is a common postmortem finding in patients who have died from advanced non Hodgkin's lymphomas (NHL). However, it rarely causes major clinical consequences, such as impairment of glomerular and tubular function, acute or rapidly progressive renal failure. Renal involvement is even less frequent as a first manifestation of NHL, the so-called "primary" renal lymphoma. A review of the main clinical, diagnostic and pathological aspects of three cases observed in our division is presented here.

Essential mixed cryoglobulinemia, type II: a manifestation of a low-grade malignant lymphoma? Clinical-morphological study of 12 cases with special reference to immunohistochemical findings in liver frozen sections.

Twelve patients with clinical and laboratory findings typical of essential mixed cryoglobulinemia, type II (EMC II) underwent multiple liver and bone marrow biopsies. In 9 of 12 cases (all hepatitis B surface antibody-negative), routine histology revealed patent infiltration of liver portal tracts, lobules and sinusoids by small lymphocytes provided with cytological characteristics closely resembling those of the LP immunocytoma of the Kiel classification. At immunophenotyping on frozen sections, these elements expressed the CD22 antigen (marker of B cells) and bore the same type of immunoglobulin (IgM/k = 8, IgM/lambda = 1) as the monotypic component in the serum. Furthermore, in 7 of 9 patients repeated bone marrow needle biopsies showed multiple foci of infiltration by plasmacytoid cells, often with paratrabecular location. In the remaining 3 cases (all hepatitis B surface and core antigen-positive), liver biopsies were consistent with a diagnosis of cirrhosis (two) or chronic active hepatitis (one). In two of them, however, Jamshidi needle biopsy evidenced bone marrow infiltrates quite similar to those observed in the other group. On the basis of these findings, the authors discuss the hypothesis that most EMC II are substained by a low-grade malignant lymphoma.

Cryodependent and cryoproducing involvement of organs in type II essential mixed cryoglobulinemia.

A review of the less frequent organ damage seen in the so-called essential mixed cryoglobulinemia, and distinguishing between cryodependent and cryofavouring organ involvement, is presented in this paper. In the first group, along with the well-known renal, cutaneous and articular lesions, the peripheral neuropathy and respiratory involvement, to date too little considered, are worthy of more accurate study. Gastroenteric and cardiac participations are rare. Among the cryofavouring manifestations of the disease, we have pointed out those affecting the liver. In our experience, however, as the immunohistochemical findings suggest, the histological patterns usually considered to be chronic persistent hepatitis are frequently an expression of a lymphoproliferative lymphoma-like process. A noteworthy percentage of lymphoid cells in the bone marrow has been found in 22 type II cryoglobulinemias after either needle puncture or osteomedullary biopsy. The histological pictures often resemble a lymphoproliferative disease. Clinical and laboratory (computerized tomographic scan) researches frequently show a moderate splenomegaly, but in none of the patients was superficial or deep lymph node enlargement found. The authors conclude by considering type II essential cryoimmunoglobulin to be a sign and a marker of a low-grade proliferative disease with rare evolution into overt lymphoma. At the same time, however, cryoimmunoglobulins themselves cause important injuries that affect the prognosis of the syndrome.

Hypocryoglobulins: a method to increase cryoprecipitation.

We used both the conventional test and a modified assay, the hypocryoglobulin test, to detect cryoprecipitates in 90 patients; 79 of them had different diseases in which cryoglobulins are frequently seen. For 11, type II essential mixed cryoglobulinemia had previously been diagnosed. It is still uncertain whether dilution of serum is a real help for detection of cryoglobulins. In the group of 79 patients, we found enhancement of cryoprecipitation in hypotonic sera in 33% of the cases, all with low cryocrit levels (less than 2%). In all but one of the patients with type II cryoglobulins, the hypocryocrit was equal to or lower than the cryocrit. The hypocryoglobulin test can detect a cryoprecipitate in patients with conventional cryocrits near the limits of visibility. In a few cases of cryoglobulinemic vasculitis, dilution of the serum can disclose a cryoprecipitate otherwise not visible.