A ring-calcified thymoma, mimicking pericardial cyst, precedes pure red cell aplasia for more than 10 years - A case-based overview of pathophysiology.

Pure red cell aplasia (PRCA) is a rare disease characterised by anaemia and low reticulocyte count, caused by absence of erythropoiesis in the bone marrow. This report describes a case of a ring-calcified thymoma that led to the development of PRCA. Moreover, we provide an overview on the classification of thymoma and the pathophysiology and treatment of PRCA.

No evidence for JAK2(V617F) mutation in monoclonal B cells in 2 patients with polycythaemia vera and concurrent monoclonal B cell disorder.

Occurrence of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN) and lymphoproliferative disorders, like B cell chronic lymphocytic leukaemia (B-CLL), in the same patient is rare. JAK2(V617F) mutation was recently introduced as a powerful diagnostic tool for Ph(-) MPN. JAK2(V617F) mutation is not present in B-CLL. In 4 previously reported patients with JAK2(V617F)-positive Ph(-) MPN and B-CLL there was no definitive proof of JAK2(V617F) mutation in B-CLL cells, although this was suggested in 1 patient. We present 2 patients with JAK2(V617F)-positive polycythaemia vera who subsequently developed a monoclonal B cell disorder. The granulocytes were separated from the mononuclear cells by centrifugation on density gradient. Using an ARIA-SORP sorter, the CD20+/CD5+ B cells were separated from the CD20+/CD5- B cells, T cells, NK cells and monocytes. On each of the fractions JAK2(V617F) mutation was analysed by allele-specific competitive blocker-PCR. In both patients JAK2(V617F) mutation was present in granulocytes confirming the clinical diagnosis of polycythaemia vera. We did not detect the JAK2(V617F) mutation in the CD20+/CD5+ B cells but detected it in CD20+/CD5- B cells, T and NK cells, indicating a lymphoid subdifferentiation of the JAK2(V617F) MPN clonality. JAK2(V617F) MPN and monoclonal B cell disorder can coexist but there is no evidence that the proliferative behaviour of these B cells is mediated through the JAK2(V617F) mutation.

[A patient with hypoaesthesia of the mandible]. / Een patiënt met hypesthesie in de mandibula.

In a patient with hypoaesthesia of the central region of the mandible, no oral cause could be found which could explain his complaint. Further examination by a neurologist and a specialist in internal medicine revealed the numb chin syndrome. The syndrome was caused by meningeal localisation of a high-grade B-cell lymphoma stade IV. After intensive chemotherapy and radiotherapy of the skull, the complaints disappeared.

Myomatous erythrocytosis syndrome: further proof for the pathogenic role of erythropoietin.

BACKGROUND: Myomatous erythrocytosis syndrome is defined by the combination of erythrocytosis, myomatous uterus and persistent restoration of normal haematological values after hysterectomy. A pathogenic role of erythropoietin is suggested by clinical and experimental data. CASE REPORT: A postmenopausal patient is described with the classical clinical signs of the myomatous erythrocytosis syndrome. During hysterectomy we demonstrated a large gradient between the erythropoietin levels in the uterine vein and artery, providing direct evidence for in vivo erythropoietin production by the myomatous uterus. CONCLUSION: While erythropoietin and its receptor are consecutively expressed in normal and myomatous uterine tissue, it is amazing that erythrocytosis occurs so rarely in such a frequent disorder as uterine myomatous. We strongly advocate cytogenetic examination of the myomatous tissue of subsequent patients with this entity.

Significance of elevated cobalamin (vitamin B12) levels in blood.

Elevated levels of serum cobalamin may be a sign of a serious, even life-threatening, disease. Hematologic disorders like chronic myelogeneous leukemia, promyelocytic leukemia, polycythemia vera and also the hypereosinophilic syndrome can result in elevated levels of cobalamin. Not surprisingly, a rise of the cobalamin concentration in serum is one of the diagnostic criteria for the latter two diseases. The increase in circulating cobalamin levels is predominantly caused by enhanced production of haptocorrin. Several liver diseases like acute hepatitis, cirrhosis, hepatocellular carcinoma and metastatic liver disease can also be accompanied by an increase in circulating cobalamin. This phenomenon is predominantly caused by cobalamin release during hepatic cytolysis and/or decreased cobalamin clearance by the affected liver. Altogether it can be concluded that an observed elevation of cobalamin in blood merits the a full diagnostic work up to assess the presence of disease.

A chromosomal abnormality in hyaline vascular Castleman's disease: evidence for clonal proliferation of dysplastic stromal cells.

The pathogenesis of the hyaline vascular variant of Castleman's disease is currently unknown; however, vascular and dendritic cell proliferations are common in this disorder. We report a clonal karyotypic abnormality (46,XX,t(1;16) (p11;p11), del(7)(q21q22),del(8)(q12q22)) in 15 of 20 cells obtained after short-term stromal cultures of a typical case of hyaline vascular Castleman's disease (HVCD). There was no histologic, immunohistochemical, or genotypic evidence of a clonal lymphoid or plasma cell proliferation supporting origin of this aberration from the stromal component, possibly dendritic cells. We re-examined 15 previous cases of HVCD and identified a spectrum of dysplastic changes in the follicular dendritic cells (FDC) of atrophic lymphoid follicles, with some cases showing expansions of FDC networks by CD21 immunostaining. We propose that localized clonal proliferations of stromal elements, particularly follicular dendritic cells, occur in typical HVCD and likely explain the increased incidence of FDC sarcomas in these patients.

Inverse relation between plasma G-CSF levels and neutrophil counts in a patient with autoimmune neutropenia treated with G-CSF.

The pharmacokinetic characteristics of granulocyte colony-stimulating factor (G-CSF) appears to be related to the neutrophil count. We report the case of an 81-year-old male with acquired antibody induced neutropenia treated with G-CSF. This produced a rapid increase in the neutrophil count which appeared to be associated with diminished trough plasma G-CSF levels. Our data appears to indicate that mature neutrophils may play a part in the clearance of G-CSF from plasma.

Parathyroid hormone-related protein (PTH-rP)-associated hypercalcemia in a patient with an atypical chronic lymphocytic leukemia.

We describe a patient with an atypical chronic lymphocytic leukemia (CLL) of the mixed cell type with a hypercalcemia due to parathyroid hormone-related protein production by the malignant B cells. On regard of the elevated serum calcium level without overt lytic bone lesions we found elevated serum levels of PTH-rP and demonstrated the presence of PTH-rP on the malignant lymphocytes. PTH-rP-related hypercalcemia in CLL is very rare. The role in PTH-rP in humoral hypercalcemia of malignancy is discussed.

Metastasis in a benign duodenal stromal tumour.

Gastro-intestinal stromal tumour (GIST) is increasingly recognized as a distinct entity within the group of soft tissue tumours. Mostly, GIST arises from the muscular components of the stromal layer, but the tumour may also originate from the autonomic nerve system, recently designated as gastro-intestinal autonomic nerve tumour (GANT). The majority of GIST is located in the stomach and small intestine; only 4% of GIST is found in the duodenum. Clinical and pathological criteria to differentiate benign from malignant GIST are not well established. Tumour size and mitotic activity are commonly considered as important features, predicting biological behaviour and outcome. It has been suggested that the clinical course of the GANT-type tumours may be more aggressive. We present a case of a radically resected duodenal stromal tumour with benign features, in a young woman, with metastases to the liver and peritoneum occurring 8 years after the initial diagnosis.

Coincidence of seminoma and sarcoidosis: a myth or fact?

A patient with a stage II seminoma of the testis was treated with a routine orchidectomy and irradiation. One and a half years later enlarged mediastinal lymph nodes were noted. Additional staging showed no other abnormalities and a mediastinoscopy was performed. The initial histologic examination confirmed the clinically suspected diagnosis of sarcoidosis. However, additional immunohistochemical analysis unexpectedly demonstrated that there was also a microscopic relapse of the testis tumor. The literature concerning the co-incidence of non-caseating granulomas and testis tumors is reviewed. It is not clear, whether the granulomas indicate the presence of genuine idiopathic sarcoidosis or whether they reflect a sarcoid-like reaction against tumor antigens. The immunopathogenesis of sarcoid formation and its possible biologic significance in obtaining a spontaneous tumor remission is discussed.

Successful excision of a pseudotumour in a congenitally factor V deficient patient.

We report a patient with congenital homozygous factor V deficiency in whom a large pseudotumour in the right upper leg was successfully surgically excised under continuous substitution with fresh-frozen plasma.

[Immune thrombocytopenia attributed to norfloxacin]. / Immuuntrombocytopenie toegeschreven aan norfloxacine.

A 65-year-old woman developed haemorrhagic diathesis due to a profound thrombocytopenia (thrombocyte count: 1 x 10(9)/l) within one week after a 10-day course of norfloxacin (2 x 400 mg/day), prescribed for cystitis. On account of increased megakaryopoiesis in the bone marrow and absence of other causes of thrombocytopenia norfloxacin-induced immune thrombocytopenia was diagnosed. No norfloxacin-dependent antibodies against platelets were detected. Treatment with prednisone (1.5 mg/kg/day) resulted in the normalization of the platelet count within 5 days.

G-CSF-induced decrease of the anti-granulocyte autoantibody levels in a patient with autoimmune granulocytopenia.

We present a case of an 81-year-old man with secondary autoimmune granulocytopenia in association with autoimmune thrombocytopenia. Treatment with granulocyte colony-stimulating factor (G-CSF) (5 micrograms/ kg/day s.c.) resulted in a rapid increase in the number of circulating granulocytes with a pronounced left shift. These changes were accompanied by up-regulation of the surface expression of Fc gamma RI (CD64) and Fc gamma RII (CD32) on the granulocytes. In addition, we noted a strong up-regulation of the Fc gamma RIII (CD16) and the activation markers CD11b and CD66b on the granulocytes. The increase in the number of circulating granulocytes was followed by a dramatic decrease in the level of cell-bound as well as circulating anti-granulocyte antibodies. It is hypothezised that the decrease in the level of cell-bound as well as circulating anti-granulocyte antibodies may be the result of an increased adsorption of the antibodies by the granulocytes.

A case of thymoma-associated autoimmune haemolytic anaemia.

A 50-year-old female presented with severe Coombs-positive haemolytic anaemia. Chest roentgenogram revealed a right-sided paracardial mass in the anterior mediastinum that was proven to be a thymoma. The patient was treated with oral prednisone (1 mg/kg/day) and subsequent thymectomy. Haemolysis did not return although the direct Coombs test remained weakly positive. In reviewing the literature 15 additional cases of thymoma-associated autoimmune haemolytic anaemia were identified.

Low-dose rIL-2-induced remission of disseminated CD30+ anaplastic large-cell lymphoma through reinforcement of presumed T-cell-mediated tumor cell killing, complicated by unilateral drowning of lymphoma-infiltrated lung.

We report on the immuno-oncologic analysis and treatment of a remarkable case of disseminated CD30+ anaplastic non-Hodgkin's lymphoma. Its clinical course was characterized by repeated spontaneous regressions, which were probably due to a T-cell-mediated anti-lymphoma immune reaction, as tumor-infiltrating T lymphocytes were consistently observed in sections of lymphoma lesions and found to express high-affinity receptors for interleukin-2 (IL-2). This marker may be particularly suitable to predict a response to low-dose recombinant IL-2 (rIL-2), as confirmed in this case by prompt lymphoma regression after regional rIL-2 perfusion of a cutaneous lesion and by an impressive overall response to systemic rIL-2 treatment. Despite the very low dose of rIL-2, 600,000 IU/24 h as a continuous i.v. infusion, systemic treatment was complicated by generalized capillary leakage and life-threatening unilateral drowning of the lymphoma-infiltrated left lung.

Unchanged pharmacokinetics of etoposide given by intra-arterial hepatic infusion as compared with i.v. infusion.

We investigated the pharmacokinetics of etoposide given to a patient suffering from multifocal liver metastases from an unknown primary tumor. The drug was given either by i.v. infusion or by hepatic arterial infusion (HAI). The calculated pharmacokinetic parameters (mean values +/- SD) were similar after i.v. infusion and HAI, viz., 6.4 +/- 0.7 versus 6.5 +/- 0.2 h for the terminal elimination half-life (t1/2 beta), 98.5 +/- 1.3 versus 101.3 +/- 5.9 mg l(-1) h for the area under the plasma concentration-time curve (AUC), 21.2 +/- 0.3 versus 20.6 +/- 1.2 ml min-1 m-2 for clearance (Cl), 17.7 +/- 1.9 versus 18.1 +/- 2.6 mg/l for the peak concentration, and 11.7 +/- 1.3 versus 11.6 +/- 1.01/m2 for the volume of distribution (Vd), respectively. We therefore conclude that administration of etoposide by HAI does not result in a significantly higher liver extraction. Hepatic extraction of etoposide is determined by the fraction of non-protein-bound (free) drug present. The lack of a difference between the two administration routes suggests that under in vivo conditions the equilibrium between free and bound drug is established before the drug reaches the hepatic arterioles. Consequently, administration by HAI does not lead to an increased exposure of the tumor in the liver to free (active) etoposide. Furthermore, the overall exposure of the liver to total (bound + free) etoposide is increased only from about 100 to 120 mg l-1 h. These results do not favor the use of this more complex route of drug administration in the treatment of (metastatic) cancer located in the liver.