Frequency and clinicopathological correlations of histopathological variants of idiopathic focal segmental glomerulosclerosis in nephrotic adolescents.

OBJECTIVE: To determine the frequency and clinicopathological correlations of focal segmental glomerulosclerosis variants in adolescents with idiopathic nephrotic syndrome. METHODS: All consecutive adolescents (12 to 18 years) who presented with idiopathic nephrotic syndrome in the period, January 2009 to December 2012, and in whom the histological diagnosis of focal segmental glomerulosclerosis was made on renal biopsies, were included in this prospective study. Their clinical, laboratory and histopathological features at the time of presentation or biopsy were noted from the case files and the biopsy reports. RESULTS: Among 50 adolescents, 34 (68%) were males and 16 (32%) females.The mean age was 15.14 +/- 2.3 years. The mean duration of disease was 6.3 +/- 11.2 months.The mean serum creatinine was 0.96 +/- 0.82 mg/dl. The mean 24-hour urinary protein excretion was 3.8 +/- 0.68 grams. Biopsy indications were steroid-resistant nephritic syndrome in 15 (30%), steroid-dependant nephritic syndrome in 19 (38%) and adolescent nephritic syndrome in 16 (32%) cases. Among the focal segmental glomerulosclerosis variants, 40 (80%) were "not otherwise specified", followed by the collapsing variant, which accounted for 8 (16%) cases. The tip and cellular variants, both were found in one (2%) case each. Among the histological features, global glomerulosclerosis was found in 23 (46%) cases, and segmental scarring/collapse in all (100%). A variable degree of tubular atrophy and interstitial fibrosis was noted in 44 (88%) cases. CONCLUSION: The results from this study indicate that the pattern of focal segmental glomerulosclerosis variants differs markedly in adolescents compared with younger children.

Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis.

Helicobacter pylori infection is an established risk factor for gastritis, gastric ulcer, peptic ulcer and gastric cancer. CagA +ve H. pylori has been associated with oxidative DNA damage of gastric mucosa but their combined role in the development of gastric cancer is still unknown. Here we compare the combined expression of cagA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in normal, gastritis and gastric cancer tissues. Two hundred gastric biopsies from patients with dyspeptic symptoms, 70 gastric cancer tissue samples and 30 gastric biopsies from non-dyspeptic individuals (controls) were included in this study and 8-OHdG was detected by immunohistochemistry (IHC). Histological features and the presence of H. pylori infection were demonstrated by Hematoxylin and Eosin (HE), Giemsa and alcian blue-periodic acid-Schiff ± diastase (AB-PAS ± D) staining. DNA was extracted from tissues and polymerase chain reaction (PCR) performed to determine the presence of ureaseA and cagA genes of H. pylori. The results showed the presence of H. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic patients, including 70 (66 %) cases of cagA + ve H. pylori. The presence of cagA gene and high expression of 8-OHdG was highly correlated with severe gastric inflammation and gastric cancer particularly, in cases with infiltration of chronic inflammatory cells (36.8 % cagA + ve, 18 %), neutrophilic activity (47.2 %, 25.5 %), intestinal metaplasia (77.7 %, 35.7 %) and intestinal type gastric cancer (95 %, 95.4 %) (p ≤ 0.01). In conclusion, H. Pylori cagA gene expression and the detection of 8-OHdG adducts in gastric epithelium can serve as potential early biomarkers of H. Pylori-associated gastric carcinogenesis.

Reticular type parotid myoepithelial carcinoma: an intriguing variant and mimicker.

Myoepithelial carcinoma, the malignant counterpart of benign myoepithelioma, is one of the rarest salivary gland neoplasms. It is composed almost exclusively of tumour cells with myoepithelial differentiation, characterized by infiltrative growth and potential for metastasis. We herein, report a case of myoepithelial carcinoma in a 50 years old male with reticular morphology. Reticular variant of myoepithelial carcinoma may be mistaken for a variety of benign and malignant epithelial and mesenchymal tumours including mixed tumour (pleomorphic adenoma), adenoid cystic carcinoma, basal cell adenoma and epithelial myoepithelial carcinoma. Complete surgical excision is the mainstay of therapy. The role of radiation therapy and chemotherapy is not yet established. Awareness of this variant is emphasized to prevent misdiagnosis.

A clinicopathologic study of primary focal segmental glomerulosclerosis in children.

There is very little information in the literature on the treatment and prognosis of primary focal segmental glomerulosclerosis (FSGS) among children in Pakistan. This is a review of 94 children (≤16 years) with a diagnosis of primary FSGS who presented to the Sindh Institute of Urology and Transplantation between 1995 and 2008. The clinical records and original renal biopsy reports were reviewed to determine demographic, clinical, laboratory and pathologic features. Renal biopsies were studied by light microscopy, immunofluoroscence and electron microscopy. Thera-peutic regimens and response to therapy were analyzed. Majority of the children (60, 63.8%) had steroid-dependant nephrotic syndrome (SDNS) and 33 (35%) had steroid-resistant nephrotic syndrome (SRNS). Cyclosphosphamide was used in SDNS, and this produced complete remission (CR) in 25/36 (69.4%), partial response (PR) in 4/36 (11%) and no response in 7/36 (19.4%) cases. Cyclosporine was used in SRNS and some SDNS children, and showed a CR in 30 (52.6%), PR in 20 (35%) and no response in seven (12.2%) cases. Tacrolimus was used in seven (7.44%) children. CR was obtained in two (28.5%) and PR in five (71.4%) cases. Renal insufficiency developed in 12 (12.7%) children. Results from this study show that majority of the children with primary FSGS at our center could achieve high rates of sustained remission with second- and third-line immunosuppressive therapies with fairly good prognosis.

Extraskeletal osteosarcoma.

A 50 years old male presented with ulcer and swelling in left leg for 2 years. X-ray showed soft tissue sarcoma and excision was done. A diagnosis of extraskeletal osteosarcoma was made. Extraskeletal osteosarcomas are rare malignant mesenchymal neoplasms. By definition, these are located in soft tissue without primary involvement of bone or periosteum. Since these tumours mimic other soft tissue tumours and tumour like conditions, radiology and histopathology along with tumour markers studies are important in diagnosis of this tumour.

Histopathological characteristics of adult renal tumours: a preliminary report.

OBJECTIVE: To determine the relative frequencies of different renal tumours in adults and to analyze the histopathologic characteristics of renal cell carcinoma and its variants in the population studied. METHODS: The study was carried out at Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from April 2004 to October 2004. All consecutive adult patients with renal tumours managed surgically with tumour nephrectomies, were included. Nephrectomy specimens were fixed in 10% formalin. Gross and microscopic examination of the specimens was done according to standard protocol. Patients' demographic and clinical data were obtained from clinical charts and the histopathological features of tumours were retrieved from biopsy reports. RESULTS: Among 50 patients, 33 (66%) were males and 17 (34%) females. Mean age was 47.9 +/- 15.1 years (range; 17 - 80 years). Most tumours were malignant: 47 (94%) vs. 3 (6%) benign. Among malignant tumours, renal cell carcinoma (RCC) was commonest; 41 (87.2%). Various subtypes of RCC included: conventional/clear cell RCC, 30 (73.2%); papillary RCC, 6 (14.6%); chromophobe RCC, 1 (2.4%) and sarcomatoid RCC, 4 (9.7%). Other malignant tumours were: rhabdomyosarcoma, 2 (4.2%); primitive neuroectodermal tumour, 1 (2.1%); transitional cell carcinoma, 2 (4.2%); and squamous cell carcinoma, 1 (2.1%). Benign renal tumours included one case each of angiomyolipoma, oncocytoma and metanephric adenoma. CONCLUSION: The spectrum of adult renal tumours in this study consistent with that of previously reported literature. RCC is the commonest malignant tumor and conventional/clear cell RCC is the most common subtype. However, RCC presentation is delayed with a large size and an advanced stage of the disease, compared to published literature.

Role of immunofluorescence and electron microscopy in the evaluation of renal biopsies in nephrotic syndrome in a developing country.

To determine the role of immunofluorescence (IF) and electron microscopy (EM) in the evaluation of renal biopsies in a developing country, the authors carried out a study in 200 patients with nephrotic syndrome. Renal biopsies were studied by light microscopy, IF, and EM. IF study was useful in all, being essential in 23.5% and helpful in remaining cases. EM was useful in 94.5% cases, being essential in 43% and helpful in 51.5% cases. The results demonstrate that IF and EM are essential in the evaluation of renal biopsies in nephrotic syndrome and these should be employed in the pathologic evaluation of renal biopsies.

Pattern of morphology in renal biopsies of nephrotic syndrome patients. Correlation with immunoglobulin and complement deposition and serology.

OBJECTIVE: To determine the morphological pattern in renal biopsies from nephrotic patients and their correlation with immunoglobulin and complement deposition as detected by immunofluorescence microscopy (IMF) and serology to arrive at correct diagnosis of glomerulonephritis (GN). METHODS: The study was carried out at the departments of Immunology and Histopathology, Sindh Institute of Urology and Transplantation (SIUT) from April 2007 to March 2008. A total of 200 patients, including children and adults were included. All patients presented with nephrotic syndrome (NS). Clinical and laboratory investigations including serology were noted, renal biopsies performed and studied by light and immunofluorescence microscopy (IMF). RESULTS: Of 200 patients, 74 (37%) were children (< or = 18 years) and 126 (63%) adults (> or = 19 years). Mean age of children was 11.34 +/- 4.85 years (range 3-18 years) and that of adults was 35.44 +/- 11.4 years (range: 19-70 years). The total percent change in L/M diagnosis after serological tests was 11.5% and after IMF studies, 23.5%. Combined serologic and IMF studies lead to 35% change in L/M diagnosis of the renal biopsies in nephrotic syndrome patients. CONCLUSION: Our results demonstrate that the ancillary techniques of IMF microscopy and serology are indispensable in the elucidation of final specific diagnosis causing nephrotic syndrome in a substantial number of cases and these should be employed routinely in the pathologic evaluation of renal biopsies. The study emphasizes the importance of combined approach in the investigation of renal biopsies in nephrotic syndrome.

Histopathological spectrum of childhood nephrotic syndrome in Pakistan.

BACKGROUND: There is no information in international literature on the pattern of glomerulopathies in children with idiopathic nephrotic syndrome (INS) in Pakistan. We undertook this study to determine the pattern of glomerulopathies based on renal biopsies studied by light (LM), immunofluorescence (IF), and electron microscopy (EM). METHODS: The study was conducted at Sindh Institute of Urology and Transplantation (SIUT), Karachi over 12 years (1996-2008). All children (

Spectrum of glomerulonephritides in adults with nephrotic syndrome in Pakistan.

BACKGROUND: There is currently little information in literature about the pattern of glomerulonephritides (GN) in adults with nephrotic syndrome in this part of the world, particularly that involving the use of immunofluorescence (IMF) and electron microscopy (EM). A few studies reported are based on light microscopic study alone and hence do not reflect the true pattern of GN underlying nephrotic syndrome. We carried out this study in the Department of Histopathology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan to determine, for the first time, the true pattern of GN in adult nephrotic patients from Pakistan. SIUT is a tertiary care center for renal and urologic disease in Pakistan. The Histopathology Laboratory of SIUT is equipped with all the modalities, including EM, required for precise diagnosis of glomerular disease. METHODS: This is a retrospective clinicopathologic study involving retrieval of clinical and pathological data from a review of original renal biopsy reports of adult patients with nephrotic syndrome who presented at the adult nephrology clinic of SIUT from July 1996 till July 2006. Two cores of renal tissue were routinely obtained. One core was fixed in 10% buffered formalin and processed for light microscopy; the other core was divided into two halves, for EM and the IMF study. RESULTS: A total of 316 adult patients were included. Of these, 201 (63.6%) were male and 115 (36.4%) were female. Mean age was 28.4 +/- 10.51 years with a range of 16-78 years. The spectrum of pathological lesions in the adult nephrotic population was wide and comprised focal segmental glomerulosclerosis (FSGS) (39.87%), followed by membranous GN (MGN) (26.58%), minimal change disease (MCD) (14.82%), mesangiocapillary GN (4.3%), mesangioproliferative GN (4.11%), post-infectious GN (2.84%), IgA nephropathy (2.53%), and other rare lesions. CONCLUSIONS: Results from this study indicate that FSGS is the single most common cause of nephrotic syndrome in adult nephrotic patients, followed by MGN, and MCD. Our data are similar to those reported in recent series from the US. The study defines the pattern of glomerular disease in adult nephrotic patients for the first time in this region, because it is based on light microscopy, serology, IMF, and EM findings.

Spectrum of pathological lesions in acute renal failure.

OBJECTIVE: To determine the spectrum of pathological lesions in percutaneous renal biopsies of patients with acute renal failure (ARF) and to compare our findings with reported literature. DESIGN: A single center based retrospective observational study. PLACE AND DURATION OF STUDY: The study was conducted in the Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi over a period of seven years (April 1995 to April 2002). SUBJECTS AND METHODS: All the patients with ARF who presented to the emergency ward of SIUT between April 1995 and April, 2002 and in whom renal biopsy was performed, were included in this study. Patient's demographic and clinical data were collected from a review of patient's original surgical biopsy reports and case files. Pathological diagnosis was retrieved from a review of biopsy reports. Renal biopsies were received in 10% buffered formalin and processed for paraffin embedding and subsequent histopathological examination under the light microscope. RESULTS: A total of 158 patients were studied. Of these 57 were males and 101 females. Mean age of the patients in this series was 30.7 years with a range of 6 to 75 years. Of these 61(38.6%) had acute tubular necrosis, 36 (22.7%) acute cortical necrosis and 49(31%) patients had various types of glomerulonephritis (GN). Eight patients (5%) had acute tubulointerstitial nephritis, 3 (1.8%) acute pyelonephritis and one patient had mucormycosis. CONCLUSION: This study showed that even in the selected population of biopsied ARF cases, there was a high prevalence of ischemic renal disease. A substantial number of cases in unexplained ARF on renal biopsy were due to various forms of glomerulonephritis.