Hypercalcemia may indicate Richter's syndrome: report of four cases and review.

BACKGROUND: Hypercalcemia has rarely been reported in patients with Richter's syndrome (RS). In this article, the authors report four cases with complementary pathophysiologic examinations. METHODS: Four patients with hypercalcemia that indicated RS were admitted to the study unit between 1980 and 1994 with the following diagnoses: transformation of mixed follicular lymphoma, Waldenstrom's macroglobulinemia, and chronic lymphocytic leukemia, respectively, in 3 men ages 60 to 73 years, and chronic lymphocytic leukemia in a woman 73 years of age. Radiologic and histologic features were reported. Circulating levels of parathormone-related peptide (PTHrP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured. RESULTS: Radiologic skeletal abnormalities were found in three of three cases: osteopenia twice and multifocal osteolysis once. All four patients had large cell lymphoma (LCL). Bone resorption assessed histomorphometrically was elevated in two of two cases. Serum TNF-alpha and IL-6 levels were high in three of three and one of three cases, respectively. Elevated values were also found in four patients with LCL but without hypercalcemia. The serum PTHrP level was increased in the only hypercalcemic patient tested and values were normal in the three control patients. CONCLUSIONS: Hypercalcemia arising in a patient with a low grade lymphoproliferative disorder may indicate RS. Hypercalcemia is due to increased bone resorption, which may be caused by the secretion of osteoclast-stimulating factors by the LCL invading the bone marrow. Independently, TNF-alpha and/or IL-6 were unlikely causative factors of hypercalcemia in the patients in this study; however, synergism with PTHrP was suspected in one case.

Plasma cell leukaemia mimicking acute monocytic leukaemia in the course of multiple myeloma.

We report a case of acute leukaemia occurring early in the course of IgA multiple myeloma. Ultrastructural studies, immunophenotyping and karyotyping were required to identify the origin and clonality of the leukaemic cells. Although ultrastructural examination of the blast cells revealed both monocytoid and plasma cell features, all cells expressed the CD 38 antigen and intracytoplasmic kappa light chains, while karyotyping revealed a clone with numerous abnormalities, leading to the diagnosis of clonal plasma cell disease. The occurrence of leukaemia in multiple myeloma is discussed.

Juvenile chronic myelocytic leukemia with unusual cytogenetic clonal evolution.

Cytogenetic studies are reported in a case of juvenile chronic myelocytic leukemia with dysmyelopoiesis and skin involvement. The clonal evolution of a 6q-anomaly is described. Hematological and cytogenetic findings suggest a role of hematopoietic stem cell in this patient for whom the outcome was fatal.

Questions concerning plasma cell leukaemia.

The classical concept of plasma cell leukaemia (PCL) is reviewed. This disease invariably concerns myeloma, either in its terminal phase (secondary PCL) or particularly rapid and aggressive (primary PCL). A more precise definition of primary PCL would be given by the term leukaemic myelomatosis. Characterization of the membrane antigen CD 56, responsible for the cytoadhesion of malignant plasmocytes in the bone marrow, today offers a convincing pathogenic hypothesis to elucidate this affection which would now appear to be no more than a variant form of myeloma. Acute immunoblastic-plasmoblastic leukaemia and mature cell leukaemic lymphoma would seem to be pathologically related to PCL. Finally, the problems posed by the "enigmatic" plasmacytoid monocyte are discussed.

[Systemic mastocytosis and malignant mastocytosis]. / Mastocytoses systémiques et mastocytoses malignes.

Systemic mastocytosis is a rare, often undiagnosed disease characterized by the proliferation of mast cells in several tissues. The clinical symptoms are related to the mast cell infiltrates, but also to the release of numerous mediators. Malignant mastocytosis is a term that refers to two different entities: aggressive mastocytosis, where the outcome with a myeloproliferative disease, where the latter governs the prognosis. The potential severity of these diseases justifies the development of more intensive therapeutic measures.

Activated partial thromboplastin time performed on capillary blood.

Activated partial thromboplastin time is one of the most frequently used assay in haemostasis investigation, but sampling of venous blood is often difficult in newborns (as well as some adult patients). We analysed a method described by Zondag et al [9] performed on capillary blood samples. We studied normal adults and newborns, patients with liver diseases, and those receiving therapy with vitamin K antagonists and heparin. Capillary assay was correlated with venous blood in normal subjects, in patients with liver diseases and during therapy by vitamin K antagonists. However results both in newborns and adults during heparin therapy were not accurate.

[Peroxidase deficiency in eosinophils: an optical and electron microscopy cytologic study apropos of a case]. / Déficit en peroxydase des éosinophiles: étude cytologique en microscopie optique et électronique à propos d'un cas.

A case of eosinophil peroxidase deficiency (EPO), discovered using an automated differential leukocyte cell counter, was studied using optical and ultrastructural cytologic methods. The blood and bone marrow eosinophilic cells had an abnormal ultrastructural aspect with important modifications of the specific granule matrix. No peroxidase activity could be revealed in these cells using optical or ultrastructural techniques. The mechanism and significance of this anomaly raise the question of the physiological function of this enzyme.

Cigarette smoking-related persistent polyclonal B lymphocytosis. A premalignant state.

A case of cigarette smoking-related polyclonal B lymphocytosis, with binucleated cells, was observed. The condition was persistent for two years. We indicated the abnormal ultrastructural features and suggest that this unexplained syndrome could be a premalignant state.

[Automation for the evaluation of blood basophilia]. / Apport de l'automatisation à l'appréciation de la basocytose sanguine.

We report here the first results of our experience in evaluating the blood basophils count through the "H 6000" automatic counter. An artefact is described through which this count may falsely be increased. The value of basophil cells rates in some diseases is being discussed.

[Alder's anomaly in mucopolysaccharidosis type VI. Cytological, cytochemical and ultrastructural study]. / Anomalie d'Alder au cours d'une mucopolysaccharidose de type VI. Etude cytologique, cytochimique et ultrastructurale.

A cytological study of the blood and bone marrow of a child with mucopolysaccharidosis with Alder's anomaly was analysed at the optical and ultrastructural level. Morphological abnormalities of the blood and bone marrow leucocytes are defined; cytochemical and cytoenzymological abnormalities are indicated, allowing a differential diagnosis with "toxic granulations". The ultrastructural patterns of the storage cells are described compared to descriptions in the literature and the question of their mastocytic or macrophagic filiation is discussed.

[Granulopoiesis in the alcoholic and cirrhotic patient. Exploration of neutropenia in cirrhosis using bone marrow cultures and a hydrocortisone test]. / La granulopoïèse chez l'alcoolique et le cirrhotique. Exploration des neutropénies dans les cirrhoses par cultures de moelle et épreuve à l'hydrocortisone.

Twenty per cent of 60 patients with cirrhosis (55 alcoholic patients) had neutropenia (defined as neutrophil polymorphonuclear (NP) count under 2,000/mm3). The authors tried to define the mechanism of this neutropenia and compared it with the acute bone marrow cytotoxicity of alcohol. They found that bone marrow neutrophil colony growth was normal in 7 cases of cirrhosis compared to 7 controls (with and without cirrhotic serum incubation). On the other hand, the granulocyte response to hydrocortisone test was less marked than in controls. This result suggests involvement of the late maturation process of NP and delayed release from bone marrow.

[Primary hemostatic disorders caused by beta-lactams. Apropos of a postoperative hemorrhagic complication during treatment with cephalexin]. / Les troubles de l'hémostase primaire dus aux bêta-lactamines. A propos d'un accident hémorragique post-opératoire au cours d'un traitement par la céfalexine.

The authors report a case of haemorrhage due to cephalexin therapy. The bleeding started after an orthopedic operation in a patient without renal failure, receiving 3 g/day of cephalexin. Platelet function was very abnormal at the time of the haemorrhage with a bleeding time of over 20 minutes, which returned to normal when treatment was stopped. This case seems to be similar to other reports of haemorrhages during treatment with other beta-lactams.

[Coexistence of myeloma and chronic myeloid leukemia]. / Coexistence d'un myélome et d'une leucémie myéloïde chronique.

The case of an eighty-one-year-old woman who had myeloma followed 18 months later by chronic myeloid leukemia with Philadelphia chromosome unrelated to therapeutic interferences is reported. This case is compared to other reports of lymphoid hemopathies associated with myeloid hemopathies found in the medical literature. The different etiopathogenic hypotheses are discussed, particularly in the light of recent studies of chromosomes. Such caryotypic studies in malignant hemopathies may improve our knowledge of the connexions between apparently dissimilar diseases and prove helpful for the understanding of cell differentiation from pathological data.

[Pure megaloblastic refractory anemia. Prolonged complete remission following androgenotherapy]. / Anémie réfractaire pure mégaloblastique. Rémission complète prolongée après androgénothérapie.

In a case of pure megaloblastic refractory anemia, a complete remission is reported. This remission has been obtained by prolonged high dose androgenotherapy and has now lasted for more than 5 years. The practical therapeutic consequences are discussed.

[Chronic lymphoid leukemia followed by acute monocytic leukemia]. / Leucémie lymphoïde chronique suivie d'une leucémie aiguë monocytaire. Etude clinique et cytologique.

A 62 year old patient with CLL treated by alkylating drugs for more than three years, underwent acute leukaemia (AL). The clinical particularities of the onset and course of this AL, the cytological, cytoenzymological and ultrastructural characteristics of the blasts are discussed in order to find a relation between the two hemopathies. A possible drug-induced etiology of this AL is proposed.

[Hypercalcemia complicating Waldenström's disease: a manifestation of Richter's syndrome]. / Hypercalcémie compliquant une maladie de Waldenström: révélation d'un syndrome de Richter.

Acute hypercalcemia occurred during the following-up of a 70 years old man with Waldenström's Macroglobulinemia (WM). Hematological data were still unchanged in spite of stopping treatment 16 months ago. It is an unusual complication in chronic lymphoproliferative disorders (except, multiple myeloma) and it was never described in the course of WM. It was related to the emergence of diffuse immunoblastic lymphoma, as it has been termed Richter syndrome in chronic lymphocytic leukemias. In WM, this occurrence is less known, but symptoms and prognostic are similar. It is to be pointed out that the spontaneous decrease of the amount of monoclonal IgM is an ominous sign of this immunoblastic transformation. The pathogenesis of hypercalcemia is discussed: the eventuality of a tumoral osteoclast activating factor is suggested.

[Malignant lymphomas and sarcoidosis (author's transl)]. / Association lymphomes malins sarcoïdose.

Five cases of sarcoidosis associated with malignant lymphoma are reported. In one patient, sarcoidosis was diagnosed several years after the onset of Hodgkin's disease. Of the remaining 4 patients, three developed nodular mixed lymphoma and one immunoblastic lymphoma (complicating angioimmunoblastic lymphadenopathy with dysproteinaemia) 3 months to 12 years after sarcoidosis were diagnosed. Such cases are extremely rare. They may be due to coincidence, but Danish epidemiological data suggest a relationship between the two diseases. Overstepping of humoral immunity in sarcoidosis may induce the emergence of a clone of formerly quiescent neoplastic B-cells.