Correlation Of Morphological Features Research Articles

#6227 SPONTANEOUS REMISSION OF MEMBRANOUS VARIANT OF PGNMID WITH MONOCLONAL IGG2κ

Abstract Background and Aims The clinical significance of the morphological patterns of glomerular injury and of each IgG subclass in proliferative glomerulonephritis (GN) with monoclonal immunoglobulin deposits (PGNMID) is not well understood. Literature suggests that PGNMID with certain histological features such as membranous or mesangio-proliferative features or non-IgG3 subclass staining may be associated with a more favourable renal prognosis. We present a patient with membranous variant of PGNMID with monoclonal IgG2κ who had spontaneous remission without recurrence over a 2-year follow-up. Method Not applicable Results A 62-year-old Malay gentleman presented with new onset nephrotic range proteinuria, on a background of type 2 diabetes mellitus with diabetic duration of 5 years, hypertension and hyperlipidemia. He was mildly hypertensive (blood pressure 148/87) and non-edematous at presentation. Investigations revealed preserved kidney function [serum creatinine (sCr) 66µmol/L], bland urinalysis, and 24-hour urinary total protein (UTP) of 3.74g/day. Serum albumin (sAlb) was 35g/L. Serum complements were not low. Autoimmune markers inclusive of anti-double stranded DNA antibodies, anti-neutrophil cytoplasmic antibodies, and anti-phospholipase A2 receptor (PLA2R) antibodies were negative. Viral serologies were also unremarkable. No monoclonal band was detected on serum electrophoresis, while serum immunofixation was not performed. Kidneys were normal sized. Renal biopsy performed demonstrated 28 glomeruli, of which only 1 was globally sclerosed. Glomeruli capillary walls were diffusely thickened by vacuolations. Capillary loops were mostly single contoured although occasional focal double contouring was seen. Masson trichome stain revealed fuchsinophilic subepithelial immune deposits while periodic acid methenamine silver stain showed argyrophilic basement membrane spikes. Variable mesangial expansion and hypercellularity was observed, as well as mesangiolysis. Focal leukocyte margination was present, but significant endocapillary proliferation was not seen. There were no Kimmelstiel-Wilson lesions. Tubular atrophy with interstitial fibrosis was overall mild (10% of parenchymal area) and there were no tubulointerstitial infiltrates. Immunofluoresence showed granular staining of IgG (1-2+), C3 (2-3+) along glomerular capillary walls, as well as presence of kappa light chain restriction (κ 1-2+; λ negative in glomeruli). Immunostaining for PLA2R was negative. IgG subclass analysis performed in view of kappa restriction revealed isolated deposition of IgG2. Electron microscopy was not available. Overall findings were most consistent with membranous variant of PGNMID with monoclonal IgG2κ. Age-appropriate and symptom-directed malignancy screening did not reveal significant abnormalities. Given that the patient was minimally symptomatic, a trial of conservative therapy was initiated with optimized non-immunosuppressive anti-proteinuric therapy using renin-angiotensin-aldosterone and sodium-glucose co-transporter-2 inhibitors. Gradual spontaneous remission was observed without recurrence over 2 years of follow-up (sCr 77µmol/L; sAlb 40g/L; 24-hour UTP 0.22g/day). Conclusion Our case adds to the literature that a membranous variant of PGNMID with monoclonal IgG2κ may be associated with better renal outcomes. Despite the lack of proliferative changes, it is possible that membranous variants may share similar underlying disease mechanisms as the other proliferative variants. Large international registries to allow the correlation of morphological features and IgG subclasses with clinical outcomes are required to confirm our observation.

Image-based analysis of trabecular bone in osteoporotic rabbits: correlation of morphological features and bone mineral density profile

Objective: To analyse a set of morphological features from digital radiographs (RX) and bone mineral density (BMD) values estimated from quantitative computerized tomography scans (QCT scans) of the knee joint of an osteoporotic rabbits, and to determine the relationship and correlation of these variables to be considered as an alternative diagnosis method. Methods: The knee joint of rabbits (N = 9 ovariectomized and injected with of methylprednisolone sodium succinate (OVX + MPSS) and 3 sham operated healthy controls) were subjected to radiographic examination before the beginning of the study and after 6 weeks; after sacrifice, they were immediately scanned with a 64-channel CT. A set of morphological features was extracted from RX images and then subjected to Principal Component Analysis (PCA); BMD-values were calculated at different depths from the articular surface of the femur and the tibia. The selected morphological variables and the BMD values were correlated in order to determine useful information in medical diagnostics. Results: Ten morphological variables explained 80.39% of the total variability, but only some of them demonstrated significant differences between baseline and OVX + SSMP states and between OVX + SSMP and control. Spearman analysis showed higher positive and negative correlation of these parameters among them (r = 0.67, 0.81, 0.83 and 1); and a moderate correlation with the BMD values (r = 0.50, 0.52, 0.52 and 0.55) during the progression of osteoporosis (OP). Conclusion: The Spearman’s rank test supported the overall significant correlation between both, the morphological features and BMD values, making them as a reliable alternative option to the diagnosis of osteoporosis.

Evidence of sympathetic innervation and α1-adrenergic receptors of the long head of the biceps brachii tendon

BackgroundThe primary purpose of this study was to investigate the sympathetic innervation of the long head of the biceps brachii tendon LHB via immunohistochemical staining for protein S-100 and neuropeptide Y (NPY) in patients with complex proximal humerus fractures, in individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC), and in cadaveric samples with no previously reported shoulder pathology. MethodsWe investigated the presence of sympathetic innervation and α1-adrenergic receptors of the long head of the biceps brachii tendon (LHB) in patients with complex proximal humerus fractures and individuals with chronic biceps tendinosis in the setting of large rotator cuff tears (RC). The correlation of morphological features with immunohistochemical evidence of neural element presence was also investigated. Forty-one LHB tendon specimens were examined. Seventeen were harvested from patients who underwent hemiarthroplasty for proximal humerus fractures, 14 were from individuals with biceps tendinosis in the context of a large RC tear, and ten were from cadaveric controls with no previous shoulder pathology. Histologic examination was performed using hematoxylin and eosin. Immunohistochemistry was used to detect the expression of the protein S-100, neuropeptide Y, and α1-adrenergic receptors, as well as to characterize the potential neural differentiation of tendon cells. ResultsA strong correlation between the expression of NPY/S-100, α1-adrenergic/S-100, and α1-adrenergic/NPY was found. The LHB tendon has sympathetic innervation and α1-adrenergic receptors in acute and chronic pathological conditions. ConclusionOur results provide useful guidance on the management of tendinosis and the handling of the LHB in hemiarthroplasties for fractures.

Proliferative glomerulonephritis with monoclonal IgG2κ deposit successfully treated with steroids: a case report and review of the literature

A novel form of glomerular injury with monoclonal immunoglobulin (Ig) IgG deposition, termed "proliferative glomerulonephritis (GN) with monoclonal IgG deposits" (PGNMID), is a recently described entity. PGNMID presents with various histological patterns, such as membranoproliferative GN, endocapillary proliferative GN and membranous nephropathy (MN). The deposits are composed of monoclonal immunoglobulin, most commonly IgG3 and occasionally IgG2. At present, the clinical significance of each IgG subclass and the morphological patterns of glomerular injury have not been fully investigated due to the limited number of PGNMID cases reported. The patient was a 27-year-old woman presenting with a mild degree of proteinuria and no other physical or serological abnormalities. Monoclonal Ig could not be identified in her serum or urine. Renal biopsy found features of MN with deposition of monoclonal IgG2κ. Electron microscopy examination revealed non-organised electron-dense deposits predominantly in subepithelial locations. Based on a diagnosis of PGNMID, she was treated with prednisolone and proteinuria significantly decreased in less than 4weeks. Although the clinical outcomes of PGNMID remain to be defined, MN features may possibly be a sign of favourable prognosis-a hypothesis supported by recent reports. The absence of advanced chronic damage in the kidney, such as glomerulosclerosis or tubulointerstitial fibrosis, may also have contributed to the favourable outcome in the present case. Further studies on additional PGNMID cases that allow the correlation of morphological features and IgG subclasses with clinical outcomes are needed in order to confirm our findings and further solidify the clinical aspects of this new disease entity.

Salivary duct carcinoma: Correlation of morphologic features by fine needle aspiration cytology and histopathology

Salivary duct carcinoma (SDC) is a highly aggressive primary salivary gland neoplasm that resembles intraductal and infiltrating breast carcinoma. To review cytomorphologic features of histology proven SDC and evaluate potential pitfalls in cytologic diagnosis. Fine needle aspiration cytology (FNAC) of five histologically proven SDCs were reviewed. One patient was an elderly male (61 years), while the other four patients were younger, in their fourth decade (average age: 38 years). The initial cytologic diagnoses in two of the cases were poorly differentiated carcinoma with differential diagnosis of SDC and high grade mucoepidermoid carcinoma, while in the third case, a possibility of malignant mixed tumor was suggested. In fourth and fifth cases, the diagnosis was suggestive of pleomorphic adenoma with cystic change. The spectrum of cytologic changes included flat sheets and cohesive papillary and three-dimensional clusters. There was moderate to severe nuclear pleomorphism and atypia. Cribriform pattern and necrosis were occasionally identified. Prominent bright granular metachromatic stroma was seen in two of the cases interpreted as pleomorphic adenoma with cystic change and in the tumor reported as suggestive of malignant mixed tumor. The fifth case showed numerous cyst macrophages and apocrine cells with mild nuclear atypia. FNAC of SDC is difficult to interpret because of overlapping cytomorphologic features. Bland cytomorphologic features in some cases and several clinical pitfalls are demonstrated in our series.

Modeling the response of the Rhine–Meuse fluvial system to Late Pleistocene climate change

We use a landscape evolution model to infer the effect of Late Pleistocene climate change on the incision–aggradation behaviour of the Rhine–Meuse fluvial system. We model the routing of runoff and sediment in the catchment in order to predict grainsize trends and the incision and aggradation behaviour in the downstream reach, where we compare it to the sequence of events and grainsize characteristics inferred from borehole corings. This sequence starts with an important incision taking place around the MIS 3 to MIS 2 climatic transition. During the coldest part of MIS 2, a coarse-grained sedimentary unit is deposited that shows an upward increase in the sand/gravel ratio. The model experiments do not predict an incision at the MIS 3 to MIS 2 transition. Therefore, the incision should be attributed to other causes, most likely effects of glacio-isostatic uplift. However, a relative upward increase in sand content of the sediments is predicted by the model. This increase is the result of the difference in transport rates between sand and gravel. Starting from a homogeneous pre-existing (MIS 3) deposit, the gravel content in the active layer increases because the sand is removed quickly and transported further downstream, whereas the gravel travels slowly and piles up with gravel originating from immediately upstream, resulting in a net accumulation. At a later stage, sand originating from much further upstream progrades fan-like over the gravelly deposits. According to the record, during the early Late Glacial warming part of MIS 2 (Bølling–Allerød interstadial), neither incision nor aggradation has taken place. This is in accordance with modelling results which show that, despite the reduction of sediment input due to re-vegetation of hillslopes, sufficient sediment remains available for fluvial transport in the channel network itself. It takes several thousands of years before effects of sediment depletion in the catchment are noted downstream. That is why we argue that the inferred incision at the late Late Glacial (the start of the Younger Dryas) in our downstream study area might reflect depletion effects related to the preceding early Late Glacial conditions. In general, our modelling results show that terraces along one large fluvial system are diachronic features. In particular, terrace surfaces are older upstream compared to downstream. In addition, complex responses to climate change are likely to occur in a large fluvial system like the Rhine–Meuse, and correlation of morphological features in the fluvial record to specific short term palaeo-climatic events, for example Dansgaard–Oeschger events could be risky without consideration of catchment (size) characteristics and associated response times.

Unlocking pathology archives for molecular genetic studies: a reliable method to generate probes for chromogenic and fluorescent in situ hybridization

Chromogenic (CISH) and fluorescent (FISH) in situ hybridization have emerged as reliable techniques to identify amplifications and chromosomal translocations. CISH provides a spatial distribution of gene copy number changes in tumour tissue and allows a direct correlation between copy number changes and the morphological features of neoplastic cells. However, the limited number of commercially available gene probes has hindered the use of this technique. We have devised a protocol to generate probes for CISH that can be applied to formalin-fixed, paraffin-embedded tissue sections (FFPETS). Bacterial artificial chromosomes (BACs) containing fragments of human DNA which map to specific genomic regions of interest are amplified with φ29 polymerase and random primer labelled with biotin. The genomic location of these can be readily confirmed by BAC end pair sequencing and FISH mapping on normal lymphocyte metaphase spreads. To demonstrate the reliability of the probes generated with this protocol, four strategies were employed: (i) probes mapping to cyclin D1 (CCND1) were generated and their performance was compared with that of a commercially available probe for the same gene in a series of 10 FFPETS of breast cancer samples of which five harboured CCND1 amplification; (ii) probes targeting cyclin-dependent kinase 4 were used to validate an amplification identified by microarray-based comparative genomic hybridization (aCGH) in a pleomorphic adenoma; (iii) probes targeting fibroblast growth factor receptor 1 and CCND1 were used to validate amplifications mapping to these regions, as defined by aCGH, in an invasive lobular breast carcinoma with FISH and CISH; and (iv) gene-specific probes for ETV6 and NTRK3 were used to demonstrate the presence of t(12;15)(p12;q25) translocation in a case of breast secretory carcinoma with dual colour FISH. In summary, this protocol enables the generation of probes mapping to any gene of interest that can be applied to FFPETS, allowing correlation of morphological features with gene copy number.

CD5-Positive B-Cell Neoplasms of Indeterminate Immunophenotype

The flow cytometric classification of CD5-positive small B-cell neoplasms is dependent largely on the differential expression of CD23 and FMC-7. Occasional CD5-positive neoplasms with prominent co-expression of these antigens are encountered, precluding definitive immunophenotypic classification. The authors studied the clinicopathologic features of 26 neoplasms with this indeterminate immunophenotype. Available morphologic material was reviewed and analysis of CYCLIN D1 derangement was performed in selected cases by a combination of immunohistochemical, molecular, and cytogenetic techniques. Individual neoplasms were classified based on correlation of morphologic features and results of CYCLIN D1 studies. The neoplasms were classified into five categories: chronic lymphocytic leukemia (14 cases), "favor chronic lymphocytic leukemia" (3 cases), mantle cell lymphoma (3 cases), lymphoplasmacytic lymphoma (1 case), and unclassifiable (5 cases). Three of the unclassifiable neoplasms had morphologic features of mantle cell lymphoma, but CYCLIN D1 derangement could not be demonstrated. Neither relative expression of CD23 and FMC-7 nor intensity of CD20 or surface immunoglobulin expression was helpful in final classification. The authors conclude that CD5-positive small B-cell neoplasms with an indeterminate immunophenotype are a heterogeneous group, requiring additional studies for final classification. The majority (65%) appear to be chronic lymphocytic leukemia, with most of the remaining cases either definitively mantle cell lymphoma or unclassifiable.

The postovulatory cat oviduct and uterus: correlation of morphological features with progesterone receptor levels.

Oviducts and uteri were obtained from cats at estrus and up to 14 days after coitus. Progesterone binding sites were estimated by Scatchard analysis, serum levels of progesterone were determined by radioimmunoassay, nd key morphological parameters of the lining of the epithelium of the oviduct and the deep uterine glands were quantitated. Progesterone cytosol binding was highest at estrus, significantly depleted by day 4, and continued a gradual decline out to day 14 in both tissues. Nuclear binding was markedly elevated at day 4; with time the binding decreased until by day 14 it was equal to or lower than that detected at estrus. The initial depletion of cytosol binding and rise in nuclear binding coincided with the initial rise in serum progesterone levels. Within the oviduct, the increase in nuclear binding coincided with the onset of regressive changes within the epithelium. These changes included atrophy, deciliation, and apoptosis. Within the uterine glands, the increase in nuclear binding coincided with the onset of the progestational response. This response included cell hypertrophy, glycogen synthesis and deposition, and with longer exposure to elevated levels of progesterone, the disappearance of these glycogen deposits. These results clearly illustrate the immediate effect of low levels of progesterone on the subcellular compartmentalization of the progesterone receptor system, and the down regulation of the total receptor system when target tissues are exposed to a continuous elevation of serum progesterone. These results also illustrate that similar changes in receptor compartmentalization induce different morphological responses within target tissues from the same animal.

Diffuse large cell lymphomas (reticulum cell sarcomas, histiocytic lymphomas). Correlation of morphologic features with functional markers.

Electron microscopic findings in 15 cases of diffuse large cell lymphoma were correlated with other morphologic features, surface immunotype and cytoplasmic immunoglobulin content. Immunologically, the cases were: B cell, 8; null, 4; T cell, 2; and H cell (true histiocytic), 1. Ultrastructurally, all B cell and three null lymphomas were characterized by an abundance of polyribosomes and segments of rough endoplasmic reticulum. Concentric rough endoplasmic reticulum was observed in 4 cases of B cell lymphoma containing cytoplasmic immunoglobulin and in a null lymphoma. In 1 case of B cell lymphoma, the diastase-sensitive, periodic-acid-Schiff-positive cytoplasm showed evidence of widely dispersed monoparticulate glycogen granules. The two T cell lymphomas contained hyperlobulated or single round nuclei, and abundant smooth to rough endoplasmic reticulum. One null lymphoma appeared to share the ultrastructural features of T cell convoluted nuclei and the cytoplasmic organelles of myeloid precursor cells. The H cell lymphoma had features of monocytic-macrophagic differentiation. The large cell lymphomas, a morphologically and functionally heterogeneous group, were represented predominantly in this series by neoplasms with follicular center cells or early plasma cells.

Fibrocystic disease of the breast: Correlation of morphologic features with the clinical course

In 794 patients with fibrocystic disease of the breast, 142 (17.9 per cent) required more than one excision over a five year period. Two groups were established, one representing clinical quiescence, the other comprising patients that had two or more operations. These groups were analyzed according to morphologic criteria, based on the degree of epithelial hyperplasia. Lesions without appreciable epithelial proliferation predominated in the patients who had undergone only one operation. Hyperplasia, moderate to extreme in degree, was present in the majority of those patients who required more than one excision. No increased incidence of carcinoma was noted in the presence of epithelial proliferation.