Veli Uysal

Lupus Nephritis in Children: Prognostic Significance of Clinicopathological Findings

Background: We aimed to review our experience with childhood lupus nephritis (LN) in respect to the analysis of the clinical and histopathological presentation of LN and prognostic factors affecting the kidney and patient outcomes. Method: Forty-three children (39 girls, 4 boys) with biopsy-proven LN were included in the study. The mean age of the children was 12.0 ± 2.8 years. Based on the renal histopathology and clinical presentation, patients were treated with oral prednisone, intravenous pulses of methylprednisolone or intravenous cyclophosphamide. The final clinical status was classified as follows: (1) renal and extrarenal remission; (2) clinically active renal disease, or (3) adverse outcome, i.e., end-stage renal failure (ESRF) or death. Results: The mean duration of follow-up was 7.2 ± 2.8 years (1 month to 14.2 years). All 43 children had hematuria and 53.5% had proteinuria at admission. Fourteen children were in nephrotic status at the onset of disease. Class IV (diffuse proliferative) nephritis was observed in 29 patients as the most frequent histopathology (67.4%). The patients with class IV nephritis had a tendency to develop nephrotic syndrome, heavy proteinuria, increased Cr levels and persistent hypertension at initial evaluation. Thirty-two of 43 children (74.4%) were in renal remission at the last visit. Five-year kidney and patient survival rates from the time of diagnosis to the endpoints of ESRF or death were 83.7 and 90.7% respectively in the whole group while it was 75.9 and 86.2% respectively in the class IV group. Adverse outcome was significantly associated with the persistent hypertension, anemia, high serum Cr level, heavy proteinuria, nephrotic syndrome and class IV nephritis at presentation. Conclusion: We can conclude that the prognosis of LN in children is primarily dependent on the histopathological lesions. Severity of the clinical renal disease at admission and presence of persistent hypertension are the main poor prognostic factors rather than age, gender, low C3 and C4 levels, ANA positivity and the treatment modalities in Turkish children.

Can renal oncocytoma be differentiated from its renal mimics? The utility of anti-mitochondrial, caveolin 1, CD63 and cytokeratin 14 antibodies in the differential diagnosis.

Among the epithelial renal tumours with eosinophilic cytoplasm, the main differential diagnostic problem arises between renal oncocytomas (ROs) and eosinophilic variants of chromophobe renal cell carcinomas (RCCs). We investigated the possible role of anti-mitochondrial (AMA), anti-caveolin 1 (CAV1), anti-CD63 (CD63) and anti-cytokeratin 14 (CK14) antibodies in the differential diagnosis of eosinophilic epithelial tumours and applied the Muller and Mowry modification of Hales colloidal iron stain (HCI). Thirty-five ROs and 77 eosinophilic RCCs (27 chromophobe, 28 clear cell and 22 papillary RCCs) were included in this study. Apical and/or polar CD63 immunostaining (94%) and diffuse AMA (91%) and CAV1 (88%) immunostainings were the characteristics of ROs, whereas diffuse CD63 immunostaining (96%) and diffuse-peripheral AMA (96%) and CAV1 (92%) immunostainings were characteristic immunohistochemical features of eosinophilic chromophobe RCCs. We showed CK14 antibody not to be useful in the differential diagnosis of the eosinophilic epithelial renal tumours. The staining localisations with AMA, CAV1 and CD63 antibodies were significantly different between tumour groups. AMA had 96% sensitivity and 94% specificity, whereas CAV1 had 92% sensitivity and 97% specificity in diagnosing chromophobe RCCs. With HCI staining, ROs, showing apical and/or polar staining, could be differentiated from chromophobe RCCs, showing diffuse cytoplasmic staining. HCI had fairly low (69%) sensitivity and 100% specificity, whereas CD63 had 95% sensitivity and 100% specificity to diagnose ROs. We recommend using CD63 as the best marker of choice for distinguishing ROs from eosinophilic chromophobe RCCs when standard diagnostic criteria are not helpful.

Impact of p53 and Ki‐67 in predicting recurrence and progression of superficial (pTa and pT1) urothelial cell carcinomas of urinary bladder

In predicting the aggressive behavior of bladder tumors, the histopathological characteristics of grade and invasive stage are of principal importance. However, for predicting tumor recurrence and progression, these are sufficient only to a limited extent, particularly in the case of superficial (pTa and pT1) urothelial cell carcinomas. New prognostic factors are therefore needed to avoid either insufficient or excessive treatment. In this retrospective study, we investigated the prognostic value of the p53 and Ki‐67 immunoreactivity indices. The present study included 118 superficial urinary bladder tumors consisting of 58 recurrent and 60 non‐recurrent cases. Twenty of the recurrent tumors progressed into a higher grade and/or invasive stage. Paraffin immunohistochemical analysis was carried out using anti‐p53 and anti‐Ki‐67 antibodies on the initial tumor tissues. We concluded that there is a highly significant relationship between the p53 and Ki‐67 immunoreactivities and the histological grade and pathological stage of the tumors (P < 0.0001). We observed a significant relationship between the presence of recurrence and progression and the p53 immunoreactivity index (P < 0.01 and P = 0.017, respectively) and Ki‐67 immunoreactivity index (P < 0.0001 and P = 0.046, respectively). Positivity for p53 and Ki‐67 can demonstrate the risk of recurrence (p53: sensitivity = 76%, specificity = 58%; Ki‐67: sensitivity = 86%, specificity = 48%) and progression (p53: sensitivity = 80%, specificity = 46%; Ki‐67: sensitivity = 85%, specificity = 36%; ). We believe that both of these immunohistochemical markers can be considered valuable in addition to classical histopathological prognostic parameters for predicting recurrence and progression risks.

Primary signet ring cell carcinoma of the urinary bladder. Review of the literature and report of two cases.

The signet ring cell carcinoma of the urinary bladder is a rare neoplasm; the 70 cases found in the literature pursued a fulminant and mostly fatal course; the neoplasms diffusely invaded the bladder wall without forming intraluminal growths and could not be controlled by segmental resection, radiotherapy and chemotherapy alone or in combination. We herewith present 2 cases of primary signet ring cell carcinoma of the urinary bladder--one associated with high-grade transitional cell carcinoma and in situ carcinoma--and review the literature.

Pulse methylprednisolone therapy in children with membranoproliferative glomerulonephritis

The effects of pulse methylprednisolone (PM) therapy were studied in 15 patients (aged 3–14 years) with biopsy proven membranoproliferative glomerulonephritis (MPGN). Patients were treated with intravenous PM 30 mg/kg (max 1 g) given over 30 min every other day for a mean of 9.8 days (3–15 days). Oral prednisolone therapy was continued at a dose of 1 mg/kg/24 h for 1 month and subsequently tapered off the following month. Eight patients had hematuria and six had medically controlled hypertension. Serum C3 levels were low in 11 patients and all of the patients had proteinuria. Following PM therapy proteinuria was significantly reduced from 2602.9 ± 1852.5 mg/24 h to 1871.2 ± 2090.8 mg/24 h (P < 0.05) and at final evaluation, proteinuria was 774.33 ± 1225.67 mg/24 h which was significantly lower than pre‐ and post‐PM therapy values (P < 0.05). Serum creatinine levels were high in five patients before PM therapy and remained high in one of the patients who progressed to end‐stage renal failure. After PM therapy, high serum creatinine levels normalized in three patients and was reduced, but still above normal, in one. One patient, with initially normal serum creatinine, had elevated levels afterwards. Nine of the patients were considered responsive and six non‐responsive according to our tentatively defined criteria. Mean follow‐up period was 27.4 ± 24.1 months (6–84 months). Three patients were lost for follow‐up, and 12 were re‐evaluated. At final evaluation, all of the patients except one with end‐stage renal failure had normal creatinine levels. There was no correlation between the clinical and laboratory features at onset and the outcome of the disease in the responder or non‐responder patients. Results of our study show that PM therapy reduced proteinuria and may affect renal function positively in patients with MPGN. However, a prospective controlled study with repeat biopsies is required to draw a conclusion.

Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of the penis

Ewing’s sarcoma/primitive neuroectodermal tumor (ES/PNET) of the penis has been very rarely defined. We report a case of a 19-year-old patient with a tumor, localized in the dorsal side of penis, composed of small round cells with diffuse membranous mic-2 (CD99) immunopositivity. The patient was treated with multiagent chemotherapy and radiotherapy.

Sarcomatoid chromophobe renal cell carcinoma with squamous differentiation

Sir, Sarcomatoid change has been found to arise in all subtypes of renal cell carcinoma (RCC). It is well known that those with a sarcomatoid component are most likely to behave in an aggressive fashion. Sarcomatoid change has been reported relatively frequently in chromophobe RCCs. Although squamous differentiation may be seen in many other tumours, it has not been reported in RCCs, especially in chromophobe RCCs. We report here a case of sarcomatoid chromophobe RCC with malignant squamous differentiation. A 60-year-old man complained of lower abdominal and right flank pain. Computed tomography and ultrasonography examinations disclosed a mass in the right kidney, and a radical nephrectomy was undertaken. The surgical specimen revealed a 1161067 cm well-demarcated mass with the central area showing necrosis and cystic degeneration in the cortical part of the kidney. The cut surface of the tumour was beige and whitish in colour and predominantly of solid consistency. Thirty representative samples were sectioned for microscopic examination. The tumour was largely composed of spindle shaped pleomorphic cells, pure-classic chromophobe RCC areas and chromophobe RCC areas with malignant squamous differentiation. Their proportions were 50, 10 and 40%, respectively (Fig. 1). The squamous component of the tumour contained also keratin foci within epithelial cells arranged in whorl-like pattern. Frequent mitosis and frank cytological atypia were present, except in areas of pure chromophobe RCC. The cytoplasm of typical chromophobe RCC areas reacted diffusely with Hales’ colloidal iron stain. Spindle shaped cells were strongly vimentin positive (Fig. 2). However, a faint pancytokeratin and epithelial membrane antigen positivity were observed in some spindle cells. Although we did not observe any other heterologeous component, we investigated immunoreactivity for S-100 protein, smooth muscle actin, desmin and CD56, but none of them were positive. Pure chromophobe RCC areas revealed strong and diffuse

FREQUENCY OF RENAL AMYLOIDOSIS SECONDARY TO TUBERCULOSIS

Osman Erk, Istanbul Universitesi, Istanbul Tip Fakültesi, Acil Dahiliye Klinigi, Çapa, Istanbul (Turkey) Dear Sir, Although tuberculosis occurs infrequently it has attracted increasing attention in recent years. In part this reflects an increased awareness of its renal complications such as amyloid deposition in the kidneys. Amyloid is often first deposited in the mesangium of the glomeruli and later extends along the basement membrane. Initially present as small focal nodules, these deposits eventually become larger, obliterate the capillary lu-mina and replace the entire tuft. Ultimately the glomeruli become atrophic and structureless and replaced by amyloid surrounded by concentric layers of collagen. Proteinuria was reported to be present in about 80% of patients and was not necessarily correlated with the extent of glomerular involvement [1]. Some investigators have noted that the severity of proteinuria correlates better with the presence of spicules and the destruction of podocytes. The greatest loss of protein probably occurs in areas where the basement membrane is disrupted by amyloid and denuded of its epithelial covering. 60% of the patients were reported to develop the nephrotic syndrome, while renal insufficiency was found in more than half of the patients at the time of diagnosis [2]. We studied the occurrence rate of tuberculosis causing renal amyloidosis. 237 patients with renal amyloidosis diagnosed by biopsies were investigated. Only 81 (35.6%) had a previous history of tuberculosis and the remaining 156 patients had amyloidosis due to other causes. Among these patients with renal amyloidosis secondary to tuberculosis, 55 (67.9%) were males and 26 (32%) were females. The mean age was 45.22 ± 3.5 years (range 21-58 years). The duration of the disease was found to vary from 1 to 6 years with an average of 2 ± 1 years. 79% of patients showed clinical manifestation of the nephrotic syndrome; only 23.4% had developed renal failure. Hepatomegaly was present in 47 (58%) and splenomegaly in 18 (22%) patients. 12 patients (14.8%) showed gastric atony, 17 patients (20.9%) emphysema and 11 patients bronchiectasis (13.5%). Pleural effusion was present in 9 cases (11.1%); 23 (28.3%) patients were hypoten-sive and 5 cases (6.1%) had peripheric neuropathy and 10 (12.3%) a fever. Laboratory findings revealed the ESR to be high in 27 (33.3%), leukocytosis in 16 (19.7%), leukopenia in 5 (6.1%), lymphocy-tosis in 3 (3.7%) and eosinophilia in 22 (27.1%) patients. In 58 (71.6%) patients the hematocrit was below 30%, and in 4 cases (4.9%) pancytopenia and in 12 (14.8%) trombocytopenia were present. In 61 patients (75.3%) αi-, c1⁄8and γ-

Should High-Grade Prostatic Intraepithelial Neoplasia Change Our Approach to Infravesical Obstruction?

Objectives: To investigate whether coexistence of high-grade prostatic intraepithelial neoplasia (HPIN) should change our therapeutic approach to infravesical obstruction. Material and Methods: Of 505 patients who underwent sextant transrectal ultrasonography (TRUS)-guided prostate biopsy, 65 (12.8%) had HPIN and 29 of them underwent prostatectomy (23 transurethral resection of prostate (TURP), 6 open) due to obstructive urinary symptoms. Patients without carcinoma were followed up with semiannual prostate-specific antigen (PSA) and digital rectal examination. After a follow-up of 24.8 ± 11.0 months, 19 of 29 patients who accepted our call had another sextant biopsy. Results: Mean age and initial mean PSA values of 29 patients were 67.6 ± 6.7 years and 9.26 ± 5.91 ng/ml, respectively. The final pathological evaluation of the surgical specimens revealed 2 prostatic adenocarcinomas both in the TURP group. The remaining 27 (93.2%) patients were found to have benign prostatic hyperplasia (BPH) and their serum PSA levels declined from 9.26 ± 5.91 to 4.59 ± 2.0 ng/ml 3 months after prostatectomy. Of the 19 patients who had another biopsy with a mean PSA value of 4.06 ± 4.61 ng/ml, 15 and 4 of them had BPH and HPIN respectively. Conclusions: Our preliminary data indicate that the presence of HPIN on TRUS-guided biopsies is not a factor to delay an indicated surgical intervention for infravesical obstruction.

Bir Mezoblastik Nefroma Olgusu

Mezoblastik nefroma; fetal renal hamartoma yenidoganin mezankimal hamartomasi leiomyomatoz hamartoma gibi degisik adlar ile de anilan bir bobrek tumorudur Yenidogan ve erken sut cocuklugu doneminde fizik muayenede batinda palpe edilen bir kitle seklinde saptanir Ek bulgu olarak hematuri hipertansiyon kusma ve sarilik gozlenebilir nbsp; Bu hastalarin tanisinda; IVP ultrasonografi ve bilgisayarli tomografiden yararlanilir Tumorun cerrahi olarak cikartilmasi ile sagilim saglanir Yenidogan doneminde mezoblastik nefroma tanisi konulan bir olgu sunularak yenidogan donemi bobrek tumorleri gozden gecirilmistir Anahtar kelimeler: Renal Tumor Yenidogan Mesablostik Nefroma