Primary localized amyloidosis of the urinary bladder. A case report.

We present case 96 (the first one in Bulgaria) of primary localized amyloidosis of the urinary bladder in a 72-year-old woman with episodes of painless hematuria. The amyloid tumor is situated on the anterior wall of the bladder--a yellowish prominence 15 mm in diameter with superficial erosion that is surrounded by a reddish ring and bullous edema of the mucosa. Rough and regularly pink perivascular deposits, thickened vessel walls and focal lymphoplasmocyte infiltrates are present in the submucosa. After preliminary treatment with KHMnO4, AL-amyloid is detected in polarized light by Congorot staining and in ultraviolet light using thioflavin. Immunoglobulins and C3 deposits are not found. On electron microscopy deposits of amyloid fibrils are seen in abundance close to collagen bundles. Diseases that may be associated with systemic amyloidosis have been clinically excluded. Nodular amyloidosis resulting from a local immune dyscrasia is accepted in the case. The patient is in good health 11 months after the first biopsy. A literature review on this rare form of localized amyloidosis has been made. Generally, the disease has a favorable prognosis and non-active behavior is recommended. Intravesical instillations of dimethyl sulfoxide, sectional resection or plastic surgery that preserve the urinary tract are used in the rare case of progressive course.

A case of undifferentiated (embryonal) sarcoma of the liver: fine needle aspiration cytology diagnosis by one cell type.

We present the first case in Bulgaria of cytologically verified undifferentiated (embryonal) sarcoma of the liver. A 10-year-old girl was admitted to the hospital with abdominal pain, extreme hepatomegaly, one-month fever, anemia and highly elevated erythrocyte sedimentation rate (95 mm). A large formation was found in the right liver lobe on ultrasound examination, which was polycystic on CT scan. Neither bone marrow abnormalities nor elevation of serum alpha-fetoprotein was found. In the scanty specimen obtained by fine-needle aspiration biopsy under ultrasound control a characteristic prevalence of polygonal cells within mesenchyme tissue was found. The cells had eccentric hyperchromic nuclei which were pushed to the periphery by large clusters of PAS-positive, diastase-resistant granules. Vimentin and alpha 1-antitrypsyn were expressed immunohistochemically. The cells are pathognomonic of undifferentiated (embryonal) sarcoma of the liver. After preoperative chemotherapy with ifosfamide, vincristine and actinomycin D (CEVAIE, CWS--96) resection of the tumor including IV, V, VI and VII liver segments was performed. A 30 x 30-cm soft gray-whitish tumor with fine capsule was found. The cytological diagnosis was histologically verified. The patient had a mechanical subileus episode after the 6th course of chemotherapy. One year after the surgery she is in good condition. The histogenesis of this rare tumor is discussed regarding its unique cytology, immunohistochemical constellation and ultrastructure. A literature review is presented. The case indicates that the unique cell appearance in embryonal sarcoma of the liver provides a correct diagnosis even in a scanty specimen.

A denture complication: sarcoid-like foreign body granulomas of the tongue.

Sarcoidosis in the oral cavity occurs extremely rare (there have been described only 47 cases in the literature) and is almost always doubtful. We describe a protruding painful nodule (1 cm) on the apex of the tongue of a 65-year-old female, adjacent to the site of irritation of a new denture. Histologically it was confluent mass of non-caseous granulomas, rich in Langhans' cells. Silver impregnation showed them stamped out as in sarcoidosis. Corticosteroids proved to be ineffective and the therapy was discontinued because of the concomitant diabetes. Six months later, similar nodules reappeared on the same place. When examined in polarized light these giant cells were found to be of the foreign body type, each of them containing phagotized particles displaying bright yellow and dark green colour. We assume a sarcoid-like reaction of traumatic origin. There was no recurrence of the condition after removal of the denture.

Primary malignant melanoma of oral cavity.

Primary oral malignant melanomas (POMM) are very rare. Definitive identification is usually possible only after they develop metastases. So every new case is instructive. P.P., a 76-year-old woman presented with a painless exophytic mass (measuring 3 x 3.5 cm) on a pedicle in the right alveolar crest of the upper jaw (teeth 6, 7 and 8) and the palate. The mass was dark red with lobate and ulcerated surface and dense and elastic consistency. Electroresection was performed until healthy tissue was reached. One year later there were enlarged lymph nodes submandibularly on the right: a metastasis arising from an achromatic melanoma of the upper jaw. Fontana-Masson staining, expression of S-100 protein in the melanocytes. The patient was in good condition two years after the administered telegamma and immunotherapy. POMM affects mainly men at advanced age. It is four times as frequent in the upper jaw and palate as it is on the surfaces. The tongue is not affected by POMM but is targeted by the melanoma metastases. Only one third of all cases of POMM are pigmented. They arise on the basis of premelanotic changes. Every equivocal pigmented lesion in the oral cavity should be obligatorily subjected to biopsy. Primary lymph dissection is not used routinely. The therapy of choice is a radical resection combined with chemical, radio and immunotherapy. Prognosis remains grave in spite of treatment.

Treatment of immune nephropathies with high doses of immunoglobulins.

UNLABELLED: The present study presents the results from the application of high doses of gamma-globulin in the treatment of immune (idiopathic and satellite) glomerulopathies. MATERIALS AND METHODS: Twenty patients were treated. Of these 12 were with primary chronic glomerulonephritis, 7--with lupus nephritis and 1--with renal amyloidosis. All diagnoses were verified through a renal puncture biopsy. The following therapeutic scheme was used--85 mg/kg/body weight of gamma-globulin was applied intravenously three times a day every other day till reaching a total course dose of 250 mg/kg/body weight. All patients presented with nephrotic syndrome following conventional treatment with corticosteroids, anticoagulants and anti-aggregants. The blood cell count, the serum creatinine, creatinine clearance, 24 h diuresis and level of proteinuria were monitored. RESULTS AND DISCUSSION: 14 of the patients showed a complete clinical and laboratory remission. Four of them got an incomplete remission with a proteinuria of 2 g/24 h. No positive effect from the treatment was observed in 2 of the patients. All patients with lupus nephritis were influenced positively to a certain extent by the treatment applied. No serious side effects leading to therapy interruption were observed. CONCLUSIONS: 1. The treatment with high doses of immunoglobulin is a good alternative to the pulse immunosuppressive treatment of patients with idiopathic and lupus nephritides, manifested with a nephrotic syndrome and unaffected by a previous conventional immunosuppressive and anticoagulant therapy. 2. The results from the treatment with high doses of immunoglobulin are more pronounced in patients with lupus nephritides, which in turn raises the possibility for an earlier reduction of corticosteroid therapy and avoidance of its side effects. 3. Immunoglobulin therapy is an alternative in the management of nephrotic symptoms in cases with chronic renal failure where an immunosuppressive treatment is irrelevant.

Cyclosporin A in the treatment of patients with nephrotic syndrome.

OBJECTIVE: To present our experience in the treatment of conventional therapy refractory nephrotic syndrome with cyclosporin A. MATERIAL AND METHODS: The study sample included 22 patients (12 men, 10 women, aged 40.43 +/- 5.93 years). Twenty one patients were diagnosed histologically: 11 were with different histologic variants of chronic gtlomerulonephritis, 7 with lupus nephritis and 3 with renal amyloidosis. Sandimmun Neoral-Sandoz was given orally in a dose of 2-5 mg/kg/24 hours; mean duration of the course of treatment 41.4 +/- 12.4 days. In the course of treatment we followed quantitatively 24-hour proteinuria, diuresis, hematologic parameters, serum creatinine, transaminases, the fat profile, and creatinine clearance. RESULTS: The patients were allocated into 3 groups according to their response to treatment--in 5 patients (22.73%) it achieved complete clinical and laboratory remission, in 8 (36.36%)--partial remission and in 9 (40.91%) it failed. The 24-hour diuresis in the patients with complete and partial remission increased significantly during the third week of treatment (from 1212.5 +/- 114.7 to 2700 +/- 394.61, p < 0.05, t = 3.62). Proteinuria was reduced from 3.47 +/- 0.54 to 1.86 +/- 0.36 g/d (p < 0.05, t = 2.48) at the end of treatment. No substantial change in the antihypertensive therapy was necessary in any of the patients. There was no decline of the renal and liver functions. Neither allergic reactions nor serious side effects that may have caused discontinuation of treatment were observed. Complete or partial clinical and laboratory remission was achieved in 59.09% (13 patients) (confidence interval = 39.2%-78.9%, odds ratio = 0.95). Cyclosporin A therapy is an appropriate alternative in the treatment of refractory nephrotic syndrome in some of the immunologic glomerulopathies. The types of glomerulopathy that are best affected are minimal-change glomerulonephritis, some of the mesangioproliferative glomerulonephritis cases and some forms of lupus nephritis. No effect whatsoever was found in cases with renal amyloidosis.

Wrist tuberculosis in cladribine--induced remission of hairy cell leukosis.

A 45-year-old man with "hand-shoulder" syndrome developing eight-months after Cladribine-induced remission of an 11-year-old hairy cell leukosis is presented. Wrist bone biopsy was performed because of failure of the algodystrophy treatment and radiographic findings of progressive osteoporosis. Caseating epiteloid granulomas abundant in Langhans cells were found histologically and later Mycobacterium tuberculosis species was isolated in culture specimen. Fistulas were formed that healed after a prolonged anti-tuberculosis therapy. The role of cellular immunity deficiency in Cladribine-treated hairy cell leukosis that predisposes to mycobacterial infection is discussed.

Ultrastructural investigation of renomedullary interstitial cells in "endocrine kidney".

In the renomedullary interstitial cells of rats with Selye's "endocrine kidney" in the phase of beginning hypertension there appeared bilateral stress hypergranulation and an ultrastructural pattern of intensive prostaglandin synthesis. In the interstitial tissue of the left medulla there appeared light and dense (fibroblast- or macrophage-like) cells. Along with the stabilization of hypertension a relative degranulation of interstitial cells in the right kidney and an absolute degranulation in the left kidney took place. Necrobiotic changes, appearing in the ischaemic kidney, reflected an exhaustion of morphological substrates of prostaglandin synthesis. The changes in the interstitial cells, possessing endocrine activity, present the decisive links in the genesis of experimental malignant hypertension in rats.