Type I Gaucher disease with severe skeletal destruction, extraosseous extension, and monoclonal gammopathy.

Extraosseous extensions of Gaucher-cell deposits simulate malignant diseases. We describe a 65-year-old male with type-I Gaucher disease, confirmed by low leukocyte glucocerebrosidase activity, high plasma chitotriosidase, and N370/L444P gene-mutations, who had severe skeletal involvement, IgG-kappa monoclonal gammopathy, and a soft-tissue mass within the left iliac muscle. Bone marrow biopsy showed heavy infiltration by Gaucher cells, and histopathology of the excised extraosseous mass revealed infiltration by Gaucher cells. Thus, malignant diseases were excluded and the diagnosis of an extraosseous Gaucher-cell extension was well documented. Our case is reported because it is very interesting and unique in the literature.

Acute intermittent porphyria and systemic lupus erythematosus: report of a case and review of the literature.

The case of a Greek woman with acute intermittent porphyria (AIP) associated with systemic lupus erythematosus (SLE) is described and the literature on this association is reviewed. The coexistence of these two diseases may be determined by unknown mechanisms or could be fortuitous.

Multiple myeloma in sickle cell syndromes.

Multiple myeloma (MM) is rare among patients with sickle cell syndromes (SCS). We describe six Greek sickle cell patients aged 56 to 65 years: five haemoglobin Sbeta+thalassaemia (HbSbeta+ (thal), one sickle cell anaemia (HbSS), who developed MM (three IgGkappa, one IgGlambda, one IgAkappa, and one IgGK-IgAK (biclonal). Our HbSbeta+thal cases, represent the first reported association of this entity with MM. Generalized bleeding diathesis, stroke, grand mal seizures, bone marrow necrosis and other clinical manifestations due to hyperviscosity aggravated by sickle cell vasoocclusion were treated by plasmaphereses and exchange blood transfusions. The increase of mean survival in SCS patients due to the current medical facilities may have an impact on the incidence of MM among them, if a pathogenetic link between the two conditions exists. All our patients carried a diagnosis of cholelithiasis which may predispose to MM; two of them progressed from a monoclonal gammopathy of undetermined significance (MGUS) to MM. Further studies are needed in order to understand the relationship between SCS and MM.

Systemic AL amyloidosis in Gaucher disease. A case report and review of the literature.

Chronic Gaucher disease [GD] in association with systemic AL amyloidosis is extremely rare. We describe a 46-year-old Greek male with chronic GD confirmed by low glucocerebroside activity in fibroblasts and N370S/L444P mutations at the cerebrosidase gene, who also had systemic AL amyloidosis diagnosed by bone marrow diffuse plasmacytosis, serum monoclonal IgA-lambda, severe total proteinuria with monoclonal IgA-lambda, Bence-Jones-lambda and amyloid deposits in bone marrow, liver, spleen and kidney biopsy specimens. Treatment with melphalan and prednizolon has dramatically decreased both levels of serum M-IgA and proteinuria and also improved the clinical symptoms of amyloidosis. He died from restrictive cardiac disease 30 months after the diagnosis of amyloidosis. Previously reported cases of GD in association with AL amyloidosis are reviewed.

Gastroscopic findings in Mediterranean Kaposi's sarcoma (non-AIDS).

The frequency and degree of gastrointestinal involvement in patients with Mediterranean Kaposi's sarcoma (non-AIDS), a newly recognized form of Kaposi's sarcoma, is unknown. Eighty-seven patients with Mediterranean Kaposi's sarcoma proven by skin and/or nodal biopsy underwent endoscopic study of the upper gastrointestinal tract. Of these, 71 (81.6%) had gastrointestinal lesions. All these patients had lesions in the stomach. Additional lesions were detected in the esophagus in 19 patients and in the proximal duodenum in 8 patients, whereas additional lesions in both the esophagus and duodenum were identified in 2 patients. The lesions were classified into 4 types according to their size, shape, and color. Most types of lesions showed characteristic discoloration, but lesions with the appearance and color of normal mucosa that histologically were shown to be Kaposi's sarcoma were also identified. The high prevalence of gastrointestinal involvement in patients with Mediterranean Kaposi's sarcoma (non-AIDS) suggests that an endoscopic examination of the upper gastrointestinal tract may be useful in non-AIDS-related forms of Kaposi's sarcoma.

HLA in familial and nonfamilial Mediterranean Kaposi's sarcoma in Greece.

Fifty-four (54) unrelated patients with Mediterranean Kaposi's sarcoma (MKS) and 8 patients members of 4 unrelated families with familial MKS were serotyped for HLA-A,B and DR antigens. The diagnosis was histologically confirmed and all patients were negative for anti-HIV antibodies. An increased frequency of HLA-B18 (44.4% vs 14.2% in the controls, p < 0.001, RR = 4.8) and HLA-DR5 (57.6% vs 37.2% in the controls, p < 0.025, RR = 2.29) was observed in the group of patients with MKS. Seven (7) of the 8 family members with FMKS possessed HLA-DR5, and the affected members in the 3 families shared a common haplotype which included HLA-DR5. These findings support the hypothesis that genetic factors linked to HLA-DR5 antigen may contribute to the pathogenesis of MKS.

Primary extramedullary plasmacytoma in the middle ear: differential diagnosis and management.

Primary extramedullary plasmacytoma (PEP) is an uncommon neoplasm of plasma cell origin which afflicts the head and neck mainly. In this study we report a rare case of a 34-year-old man who presented with left ear tinnitus, hearing loss, blocked feeling and headache. Exploratory tympanotomy revealed a mass extending into the attic and the mastoid antrum. Following canal wall-up mastoidectomy, the tumour was carefully removed. Histological examination (including immunoperoxidase staining) and thorough clinical, laboratory and radiological evaluation revealed an exclusively cytoplasmic monoclonal IgG immunoglobulin PEP. The combination of surgery (including a second-look procedure) and radiotherapy used in this case may be an over-treatment. However, the patient is still disease-free seven years after his first admission to hospital.

Ras, C-myc and C-erbB-2 oncoprotein expression in non-AIDS Mediterranean Kaposi's sarcoma.

We have studied ras p21, c-myc p62 and c-erbB-2 oncogene expression in fourteen Greek patients with NON AIDS Mediterranean Kaposi's sarcoma using immunohistochemical analysis. Elevated expression of ras p21 expression was observed in all 14 cases studied (8 of which had intense levels of staining), whereas expression of c-myc and c-erbB-2 was less frequent, (6 out of 13 cases tested showed elevated c-myc expression and 6 out of 13 showed elevated c-erbB-2 expression). This report indicates that aberrant ras p21 oncogene expression is a feature of Kaposi's sarcoma and may be important in the early stages of this disease.

Endemic Kaposi's sarcoma in human immunodeficiency virus type 1-seronegative persons: demonstration of retrovirus-like particles in cutaneous lesions.

In 1984, Greek physicians reported on the clustering of cases of Kaposi's sarcoma (KS) on the Peloponnesus peninsula. To gain more insight into its pathogenesis, we studied the seroepidemiologic and clinicopathologic characteristics of 12 Greek KS patients (eight male/four female) five of whom were residents of an endemic area on the Peloponnesus. These patients were in good general health with ages ranging from 48 to 80 years, had no clinical signs of immunodeficiency, and combined the features of both classic and epidemic KS in that they displayed not only involvement of acral areas but also widespread mucocutaneous lesions. Routine laboratory data were within normal limits; no patient had HTLV-1 and HIV-1/2 antibodies, but all patients had antibodies to several herpesviruses. The histopathology was characteristic of KS with the peculiar feature of a dense infiltrate composed predominantly of CD4+ T lymphocytes. Immunoenzymatic/morphologic studies of the KS cells were consistent with their origin from lymphatic endothelium. Outstanding ultrastructural findings were tubuloreticular structures and cylindrical confronting cisternae, structures that are indicative of an ongoing viral infection. Indeed, extensive electronmicroscopic studies resulted in the detection of retrovirus-like particles in close association to KS cells in five of 12 patients. This in situ observation opens the possibility that this retro-virus contributes to KS development.

Histocompatibility antigens HLA-A, -B, -DR in Greek patients with Kaposi's sarcoma.

Thirty-two Greek patients with histologically documented Kaposi's sarcoma, aged 46 to 82 years, were typed for HLA-A, B and DR antigens. None of them was homosexual and they had not been subjected to any immunosuppressive therapy. The study revealed a significant increase of HLA-DR5 (53.1% vs. 21.4%, R.R. 4.1) and a decreased frequency of HLA-DR1 (3.3% vs. 16.6%, R.R. 0.16). An increased frequency of HLA-B18 was also noted (43.7% vs. 20.7% R.R. 2.96). These results indicate that the same positive association with HLA-DR5 antigen is observed in Greek patients as in other patients of Mediterranean origin and support the view that HLA linked factor(s) may have a role in the development of the disease.