Role of immunoflourescence in the diagnosis of glomerulonephritis.

OBJECTIVE: To correlate the findings of immunoflorescence (IF) with morphology in renal biopsies of patients with glomerulonephritis (GN) of both primary and secondary nature. METHODS: The cross-sectional analytical study was conducted at the Shifa International Hospital's Department of Pathology form March 2007 to August 2008, during which a total of 207 renal biopsies were done. Of them, the study included 92 cases which were diagnosed as primary or secondary glomerulonephritis under light microscope. Those cases were selected in which both light microscopy (LM) and immunoflorescence were done. RESULTS: Of the 92 patients, 79 (85.8%) were adults (> or = 19 years) and 13 (14%) were children (< 19 years). The mean age of adults was 36.44 +/- 11.55 (range 19-69 years) and that of the children was 10.54 +/- 3.85 years (range 4-18 years). immunoflorescence changed the morphologic diagnosis in 20 (21.73%) cases. The pattern of disease was: membranous glomerulonephritis in 24%, focal segmental glomerulosclerosis (FSGS) in 18.4%, mesangiocapillary glomerulonephritis in 2%, and minimal change disease (MCD) in 16% of the cases. CONCLUSION: Light microscopy alone can misdiagnose renal disease. This is especially important in cases of early stage membranous, IgA nephropathy (IgAN), Lupus nephritis and IgM nephropathy (IgMN), as these entities can only be diagnosed by correlating the microscopic, immunoflorescence findings and clinical details.

Primary Breast Mucinous Cystadenocarcinoma and Review of Literature.

Mucinous cystadenocarcinoma of the breast is a rare primary breast carcinoma having distinct clinical behavior and a favorable prognosis. It has a characteristic morphology that must be differentiated from metastatic ovarian and pancreatic mucinous adenocarcinoma. The etio-pathogenesis, genetic profile, and treatment of this tumor are controversial. Here, we report a case of primary mucinous cystadenocarcinoma of the breast in a 61-year-old female. The case is of interest since it is uncommon and has peculiar clinical and morphological features.

Renal Amyloidosis: A Clinicopathological Study From a Tertiary Care Hospital in Pakistan.

Introduction Systemic amyloidosis can affect any organ in the body, but the kidney is the most commonly involved site. It is characterized by the extracellular deposition of insoluble fibrillar proteins. Amyloid deposits can be identified histologically by Congo red stain, which gives apple-green birefringence under polarized light. Typing of renal amyloidosis is done by direct immunofluorescence on frozen tissue. The most common types of amyloidosis seen in renal tissue are amyloid light chain (AL) primary amyloidosis and amyloid A (AA) secondary amyloidosis. Although primary amyloidosis is considered the most common type in western countries, however, in the subcontinent region, secondary amyloidosis is more common. The spectrum of signs and symptoms in renal amyloidosis is variable including isolated proteinuria, nephrotic syndrome, hypertension, hypotension, and renal insufficiency. The present study aims to evaluate the incidence and aetiology of various types of renal amyloidosis, determine their distribution within the kidney, and study various clinicopathological features. Objective The present study aims to evaluate the aetiology and clinicopathological profile of renal amyloidosis, determine its various types, and their distribution within the kidney. Materials and methods This retrospective cross-sectional study was conducted from 1st January 2013 to 31st December 2020 at the Department of Histopathology, Shifa International Hospital (SIH), Islamabad. All renal biopsies diagnosed as renal amyloidosis were included in the study. Data were analysed using SPSS version 23 (IBM Corp., Armonk, NY). Frequency and percentages were calculated for qualitative variables, and mean and standard deviation were calculated for quantitative variables. Results A total of 131 cases were diagnosed with renal amyloidosis during the study period of eight years (from 1st January 2013 to 31st December 2020) at SIH. The age range varied from 17 to 82 years. The mean age of the patients was 45 ± 16.33 years. Out of 131 patients, 82 (62.6%) were males and 49 (37.4%) were females. Amongst them, 72 (54%) cases were diagnosed with secondary AA amyloidosis and 16 (12%) cases were diagnosed with primary AL amyloidosis. The rest of the cases 43 (34%) were of indeterminate type. The associated conditions in secondary amyloidosis were tuberculosis in 41 (57%), rheumatoid arthritis in 16 (22%), ankylosing spondylitis in five (7%), lymphoma in three (4%), diabetes in two (3%), and chronic osteomyelitis, chronic heart disease, hepatitis, and vasculitis in one case each (1.7%). Out of 16 cases reported with AL amyloidosis, 10 cases (62.5%) had a history of multiple myeloma. The most common clinical presentation was nephrotic syndrome followed by subnephrotic proteinuria, renal failure, and hypertension. Conclusion The findings of the present study show underlying etiological factors and clinicopathological characteristics of renal amyloidosis. AA amyloidosis is the most common type of renal amyloidosis in our study and tuberculosis is the most common aetiological factor. AL amyloidosis is less frequent in our population.

Variants of renal cell carcinoma; an experience at a single centre in Pakistan.

Renal cell carcinomas (RCC) have been considered as a single entity, until recently. Today, however, these are not considered as a single tumour but instead represent various distinguishable entities, each having unique histology, cytogenetic and molecular features. The variants of renal cell carcinoma can be easily recognized histologically and hence one can identify tumours having similar clinical course, morphology, genetics, prognosis and possibly treatment. This descriptive study carried over a period of one and a half year at Shifa International Hospital, Islamabad, focuses on presenting our data of various variants of renal cell carcinoma and the need for their recognition as the correct diagnosis may help to modify the therapeutic protocol. During the study period a total of 13 cases of RCC were diagnosed with the clear cell variant as the most frequent type (n=9; 69.2%). There was one case each of chromophobe renal carcinoma, medullary carcinoma, mucinous tubular and spindle cell carcinoma and multilocular cystic renal carcinoma. The average size of tumour ranged from 2.8 cm to 9.0 cm. Furhman's nuclear grade 2 was most frequently encountered (n=6; 46%) while the most frequent pathologic tumour stage was pT2 (n=7; 54%). This series is limited due to small sample size. More such studies on a larger scale with incorporation of follow up data are recommended to obtain population based statistics and identify biologically favourable variants in which nephron sparing surgery may be a suitable option.

Intraoperative frozen section analysis of sentinel lymph nodes in breast carcinoma patients in a tertiary hospital in Pakistan.

Intraoperative evaluation of sentinel lymph nodes has become routine in many units that manage early breast carcinoma. The procedure is associated with minimal morbidity and can be cost effective, avoiding re operation and reducing hospital stay as an axillary clearance can be performed under the same anesthetic after a positive intraoperative diagnosis without awaiting conventional paraffin histology. In negative cases extensive axillary lymph node dissection and its associated side effects can be avoided altogether. With careful patient selection, the expertise of surgeons and pathologists can increase the sensitivity and specificity of the technique with a reduction in false negatives. A number of international studies have established the usefulness of intraoperative sentinel lymph node evaluation. However, no local study has assessed the accuracy of frozen section in evaluating sentinel lymph node biopsy. The purpose of our study was to compare the two techniques (frozen section versus conventional paraffin histology) of the sentinel lymph node examination and to present our local data highlighting its usefulness and pitfalls, comparing the results with those in published studies. From the results obtained, we strongly recommend intraoperative assessment of the sentinel lymph nodes in breast carcinoma patients; frozen section microscopy can be a reliable and accurate technique in the hands of an experienced histopathologist.

Adult polycystic kidney disease: a disorder of connective tissue?

Adult polycystic kidney disease (APCKD) is one of the most common serious inherited disorders. Many affected patients succumb to the renal and non-renal manifestations of this autosomal dominant disease. The disease is characterized by cyst formation in several organs, most obvious of which is in the renal parenchyma. Other features associated with the disease include hepatic fibrosis, hepatic, pancreatic and splenic cyst formation, Berry aneurysms, colonic diverticulae, hernias and cardiac valvular disorders. Rupture of Berry aneurysm is a sudden and often fatal manifestation in some unsuspected cases of APCKD. We recently examined one surgically removed kidney from a 15-year-old male patient with APCKD. In addition to the classical cystic change, extensive changes in renal parenchymal matrix and vasculature are also present. The excessive and weak matrix may contribute to dilatations of both renal tubules giving rise to cysts and the blood vessels. Our findings suggest that APCKD may be a connective tissue disorder in which alteration of extracellular matrix may be a common denominator for the manifestations and organ pleotropism of APCKD.

Giant cell tumor of bone: a neoplasm or a reactive condition?

Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone tumor of young adults. It typically presents as a large lytic mass at the end of the epiphysis of long bones. Grossly it is comprised of cystic and hemorrhagic areas with little or no periosteal reaction. Microscopically areas of frank hemorrhage, numerous multinucleated giant cells and spindly stromal cells are present. Telomeric fusions, increased telomerase activity and karyotypic aberrations have been advanced as a proof of its neoplastic nature. However such findings are not universal and can be seen in rapidly proliferating normal cells as well as in several osseous lesions of developmental and/or reactive nature, and the true neoplastic nature of GCTB remains controversial. The ancillary studies have generally not reached to the point where these alone can be taken as sole diagnostic and discriminatory criteria. While giant cells and stromal cells have been extensively studied, little attention has been paid to the overwhelming hemorrhagic component. If examined carefully intact and partially degenerated red blood cells are almost invariably seen in many giant cells as well as in the stroma. While hemorrhage in many patients may be resolved without leaving any trace over time, in some it gives rise to giant cell formation, and in others it may lead to proliferation of fibroblasts and histiocytes. At times one sees xanthomatous cells due to intracytoplasmic cholesterol deposits and sharp cholesterol clefts. Individual genetic makeup, local tissue factors as well as the amount of hemorrhage may play a key role in the final effects and outcome. Malignancy usually does not occur in GCTB and when discover, it usually represents primary bone sarcomas missed at original diagnosis. Embolization therapy to curtail hemorrhage and insertion of cement substance to support matrix are helpful in reducing recurrences. Aneurysmal bone cyst (ABC) shares many features with GCTB. There had been unique karyotypic changes in some aneurysmal bone cysts making it distinct from GCTB. However these changes may be in the endothelial cells which are quite different from stromal or giant cells. It had been concluded that the poor matrix support to the vessels may lead to frequent and profuse intraosseous hemorrhage attracting blood-derived monocytes with active conversion into osteoclasts, resulting in GCTB formation. On the other hand, dilatation of the thin-walled blood vessels results in formation of ABCs. If hemorrhagic foci are replaced by proliferation of fibroblasts and histiocytes, then a picture of fibrous histiocytic lesion is emerged. Enhanced telomerase activity and karyotypic aberrations may be necessary for rapid division of the nuclei of the giant cells in order to be able to deal with significant in situ intraosseous hemorrhage.