At The Christie the Pathology Departments include Biochemistry, Blood Transfusion, Oncology Cytogenetics, Haematology and Histopathology. This collection comprises research produced by Biochemistry, Pathology and Histopathology.

Recent Submissions

  • Response of ETV6-FLT3-positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3.

    Walz, C; Erben, P; Ritter, M; Bloor, Adrian; Metzgeroth, G; Telford, Nicholas; Haferlach, C; Haferlach, T; Gesk, S; Score, J; et al. (2011-08-25)
    Imatinib-resistant tyrosine kinase (TK) fusions involving FGFR1, JAK2, or FLT3 are rare but recurrent in patients with eosinophilia-associated neoplasms. We report here 2 male patients with ETV6-FLT3(+) myeloid/lymphoid neoplasms with eosinophilia who were treated with the multitargeted TK inhibitors sunitinib and sorafenib. Patient 1 achieved rapid complete hematologic response and complete cytogenetic response after 3 months of taking sunitinib. A secondary blast phase caused by clonal evolution was diagnosed after 6 months. He achieved a second complete hematologic response after taking sorafenib but relapsed 2 months later. An N841K point mutation within the TK domain of FLT3, previously reported in acute myeloid leukemia and potentially conferring resistance to sorafenib, was subsequently identified. Patient 2 was heavily pretreated according to the initial diagnosis of T-lymphoblastic lymphoma and died in sunitinib-induced pancytopenia. This report highlights the importance of a careful diagnostic workup for eosinophilia-associated neoplasms to evaluate the possibility of TK inhibitor therapy.
  • Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma.

    Ghosal, N; Mais, Kathleen L; Shenjere, Patrick; Julyan, Peter J; Hastings, David L; Ward, Timothy H; Ryder, W David J; Bruce, I; Homer, Jarrod J; Slevin, Nicholas J; et al. (2011-10)
    Patients with adenoid cystic carcinoma of the salivary glands show over-expression of KIT in a high proportion of cases. Options for systemic treatment are limited in locally advanced and metastatic disease. We explored the efficacy of imatinib and cisplatin combined in this group of patients. A Gehan's two-stage, phase II trial was conducted on 28 patients. Those with progressive, locally advanced, and metastatic disease with an over-expression of KIT were treated with single agent imatinib 800 mg daily for two months, followed by a combination of imatinib 400mg daily and cisplatin 80 mg/m(2) at four-weekly intervals for six cycles. This was followed by maintenance single agent imatinib 400mg daily until the disease progressed. Response was monitored using fluorodeoxyglucose positron emission tomography (FDG-PET) and morphological imaging using computed tomography, magnetic resonance, and chest radiographs (CT/MRI/CXR). Morphological imaging showed partial response in three of 28 patients, and five patients showed a response on FDG-PET. In addition, 19 patients had useful stabilisation of disease. The median time to progression and overall survival was 15 months (range 1-43) and 35 months (range 1-75), respectively. The combination of imatinib and cisplatin was reasonably well tolerated. This combination may provide stabilisation in locally advanced and metastatic adenoid cystic carcinoma of the salivary glands.
  • Comparison of serum cortisol measurement by immunoassay and liquid chromatography-tandem mass spectrometry in patients receiving the 11β-hydroxylase inhibitor metyrapone.

    Monaghan, Phillip J; Owen, L J; Trainer, Peter J; Brabant, Georg E; Keevil, B G; Darby, Denise; Biochemistry Department, The Christie NHS Foundation Trust, Withington, Manchester M20 4BX, UK. (2011-09)
    The accurate measurement of cortisol by immunoassay is compromised by the potential for cross-reactivity of reagent antibodies with structurally related steroids present in serum. This susceptibility is potentiated when normal steroid metabolism is altered pharmaceutically by antisteroidogenic drugs utilized in the management of Cushing's syndrome to moderate cortisol production. The clinical implications of falsely elevated cortisol results include over-treatment and unrecognized hypoadrenalism. To investigate the effect of the 11β-hydroxylase inhibitor metyrapone on serum cortisol assay, a comparison of measurement by immunoassay versus liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted.
  • A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker.

    Khoja, Leila; Backen, Alison C; Sloane, Robert; Menasce, Lia P; Ryder, W David J; Krebs, Matthew G; Board, Ruth E; Clack, G; Hughes, A; Blackhall, Fiona H; et al. (2012-01-31)
    Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study.
  • Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches.

    Krebs, Matthew G; Hou, Jian-Mei; Sloane, Robert; Lancashire, Lee J; Priest, Lynsey; Nonaka, Daisuke; Ward, Timothy H; Backen, Alison C; Clack, Glen; Hughes, Andrew; et al. (2012-02)
    Epithelial circulating tumor cells (CTCs) are detectable in patients with non-small cell lung cancer (NSCLC). However, epithelial to mesenchymal transition, a widely reported prerequisite for metastasis, may lead to an underestimation of CTC number. We compared directly an epithelial marker-dependent (CellSearch) and a marker-independent (isolation by size of epithelial tumor cells [ISET]) technology platform for the ability to identify CTCs. Molecular characteristics of CTCs were also explored.
  • Intra-abdominal Clear-Cell Sarcoma: A Report of 3 Cases, Including 1 Case With Unusual Morphological Features, and Review of the Literature.

    Shenjere, Patrick; Salman, W D; Singh, M; Mangham, D C; Williams, A; Eyden, Brian P; Howard, N; Knight, B; Banerjee, Saumitra S; The Christie NHS Foundation Trust, Manchester, UK. (2011-11-13)
    Clear-cell sarcoma (CCS) is a soft-tissue neoplasm that morphologically resembles cutaneous malignant melanoma but has a distinct molecular profile. Gastrointestinal and intra-abdominal CCSs are very rare. Here, the authors present 3 cases of intra-abdominal CCS and review the literature. Of these cases, 2 involved the small bowel, and 1 involved the peritoneum. Cases 1 and 3 had the characteristic CCS morphology, but case 2 was morphologically unusual and therefore difficult to diagnose. It had relatively small cells with less prominence of clear cells; many pseudoglandular structures were also present. It also showed aberrant expression of epithelial membrane antigen (EMA). The other 2 cases also involved some diagnostic uncertainty and were therefore referred to specialized centers. The authors wish to emphasize the importance of molecular studies in making a conclusive diagnosis of intra-abdominal CCS.
  • Presence of monoclonal T-cell populations in B-cell post-transplant lymphoproliferative disorders.

    Ibrahim, H; Menasce, Lia P; Pomplun, S; Burke, M; Bower, M; Naresh, K; Department of Histopathology, Hammersmith Hospital, Imperial College, London, UK. (2011-02)
    As has been previously shown, the lack of immune surveillance plays a major role in the unchecked proliferation of Epstein-Barr virus (EBV)-infected B cells in the pathogenesis of B-cell post-transplant lymphoproliferative disorders. We hypothesised that the lack of immune surveillance should possibly also affect T cells, and this should lead to subsequent emergence of T-cell clones. The presence of both B- and T-cell clones in post-transplant lymphoproliferative disorders samples has rarely been demonstrated in the past. We systematically evaluated 26 B-cell post-transplant lymphoproliferative disorder, 23 human immune deficiency virus-associated B-cell lymphoma and 10 immune-competent diffuse large B-cell lymphoma samples for B- and T-cell clonality (polymerase chain reaction and heteroduplex analysis using BIOMED-2 protocol), T-cell subsets (immunohistochemistry) and EBV association (in situ hybridisation using EBER). One-half of B-cell post-transplant lymphoproliferative disorders showed evidence of monoclonal T-cell expansion, and among the T cells present in the tissue samples, CD8-positive cells predominated. Although 9/13 (69%) B-cell post-transplant lymphoproliferative disorders with the presence of monoclonal T-cell population had a CD4:CD8 ratio of ≤0.4, 0/13 of the cases without monoclonal T-cell expansion had a ratio ≤0.4 (P = 0.002). Only 2/26 (8%) demonstrated significant cytological atypia in the CD3/CD8-positive cells. There was no association between EBV and presence of T-cell clones. T-cell clones were not identified in lymphomas other than B-cell post-transplant lymphoproliferative disorders. Among 53.8% cases of EBV-positive B-cell post-transplant lymphoproliferative disorders with associated clonal expansion of T-cells tested, none had EBV-positive T cells. We conclude that half of B-cell post-transplant lymphoproliferative disorders are associated with clonal expansion of CD8-positive T cells, most of which do not amount to the coexistence of a T-cell post-transplant lymphoproliferative disorders.
  • Primary pulmonary osteosarcoma: a report of 4 cases and a review of the literature.

    Shenjere, Patrick; Travis, William D; Franks, Teri J; Doran, Helen M; Hasleton, Philip S; Department of Histopathology, Christie Hospital, Wilmslow Road, Manchester, United Kingdom, (2011-04)
    Primary pulmonary osteosarcoma is very rare. Most cases are secondary deposits from primaries arising in the appendicular skeleton. Four cases of primary osteogenic sarcoma of the lung are described and the literature reviewed for previously reported cases. These pulmonary tumors occur in patients who are in their fourth to seventh decades, that is, an older age group than their primary bone equivalent. There is a slight male predominance. There appears to be a propensity for the left lung, especially the left upper lobe. The clinical presentation is similar to primary (epithelial) lung cancer. Differentiation from pleomorphic carcinomas and other sarcomas is discussed. We know of no predisposing factor(s) in our cases for the development of this tumor.
  • Gastrointestinal stromal tumor with structures resembling intracytoplasmic lumina.

    Xu, X; Eyden, Brian P; Hou, W; Chen, T; Department of Pathology, Fudan University Cancer Center, Shanghai, China. (2010-10)
    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gut. It is characterized by positive immunostaining for CD117, and bears mutations in the c-kit or PDGFRA genes. Its origin remains uncertain. GISTs mainly possess primitive smooth muscle or neuronal differentiation. Although an epithelioid pattern of GIST is a common finding on light microscopy, true epithelial differentiation has never been demonstrated by either immunohistochemistry or ultrastructural study. Here the authors report an epithelioid GIST of the stomach, immunopositive for CD117, DOG1.1, CD34, and PDGFRA, with slight cytoplasmic staining for epithelial membrane antigen. One heterozygous mutation on codon 842 of exon 18 of the PDGFRA gene was also found. Ultrastructurally, tumor cells had plentiful organelles, including some membrane-bound, dense-core granules and cytoplasmic vacuoles. Intermingled thin cellular processes were also found. Unusually, there were many structures resembling glandular epithelial intracellular lumina with processes. The processes, although resembling microvilli, did not have filament cores, while the lumina were either empty or contained some dense or flocculent content of uncertain nature. True intracellular lumina are very rare in GIST and the authors present findings related to this issue, with a discussion on their nature, origin, and significance.
  • Epstein-Barr virus (EBV) genotypes among human immunodeficiency virus (HIV)-related B-cell lymphomas and B-cell post-transplant lymphoproliferative disorders (B-PTLD)--late-onset lymphomas, especially in the HIV setting, are associated with type-B-EBV.

    Ibrahim, H; Menasce, Lia P; Pomplun, S; Burke, M; Bower, M; Naresh, K; Departments of Histopathology, Hammersmith Hospital and Imperial College, London, London, UK. (2010-09)
    We investigated 26 B-cell post-transplant lymphoproliferative disorders (B-PTLD) and 15 human immunodeficiency virus-related aggressive B-cell lymphomas (HIV-BCL) from England that were associated with Epstein-Barr virus (EBV) for the polymorphic sequences of the EBV-encoded nuclear antigen 3C (EBNA3C) gene to distinguish the two different EBV strains. Type-A-EBV was identified in 92% of B-PTLDS and in 53% of HIV-BCL (P = 0.003). Among HIV-BCL, patients associated with type-B-EBV had been HIV positive for significantly longer when compared to those associated with type-A (P = 0.037) although there were no correlations with ethnicity, CD4 cell counts or plasma HIV viral load.
  • The accuracy of the sentinel node procedure after excision biopsy in squamous cell carcinoma of the vulva.

    Crosbie, Emma J; Winter-Roach, Brett; Sengupta, Partha; Sikand, Kanwal A; Carrington, Bernadette M; Murby, Brian; Slade, Richard J; Department of Gynaecological Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. (2010-12)
    INTRODUCTION: Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatment-related morbidity in vulval cancer patients. A prospective study was conducted to determine the diagnostic accuracy of the Sentinel Lymph Node (SLN) procedure in vulval cancer patients referred following either diagnostic or excision biopsy. METHODS: Patients with clinical stage I and II squamous cell carcinoma of the vulva underwent SLN identification with peri-scar/lesional injection of (99m)Technetium-labelled nanocolloid (pre-operative lymphoscintigraphy and intra-operative use of a hand-held probe) and intra-operative blue dye. Radical excision of the vulval tumour or scar and formal inguinofemoral lymphadenectomy was then performed as necessary. SLN were processed separately and further examined at multiple levels to exclude micrometastases (H&E/cytokeratin staining) if negative on routine analysis. Clinical follow-up was carried out to identify and treat recurrences or treatment-related morbidity. RESULTS: Thirty-two women took part. Fifteen were referred following excision biopsy and seventeen following diagnostic biopsy of their primary vulval tumour. One or more SLN was successfully detected intra-operatively in 31 patients (97%) and 45 groins. An SLN could not be identified intra-operatively in one case (re-excision of scar). On average, more SLN were identified in patients with their primary vulval lesion in situ compared with those whose tumour had previously been excised (2.6 vs. 1.8, p = 0.03). Midline tumours were more likely (15/17) than lateral tumours (1/15) to have bilateral SLN identified pre-operatively. Two patients with midline tumours previously excised had unilateral SLN. Seven patients (23%) and ten groins had inguinofemoral lymph node metastases. The SLN procedure correctly identified inguinofemoral metastases in six patients (nine groins). In one case (midline tumour, re-excision of scar) the sentinel node was positive on one side but false negative on the other. CONCLUSIONS: The SLN procedure may be used to identify malignant groins in selected patients with vulval cancer. The extent to which previous vulval surgery might influence the accuracy of the SLN procedure deserves further investigation.
  • Intraparenchymal myofibromatosis of the brain in an adult: report of an unusual case.

    Xiao, Hua-Liang; Eyden, Brian P; Yan, Xiao-Chu; Wang, Yi; Zhang, Rong; Bian, Xiu-Wu; Institute of Pathology, Southwest Hospital, Chongqing, China. (2010-06)
    An unusual case of intraparenchymal myofibromatosis of the brain occurring in a 29-year-old woman is described. Preoperative CT and MRI examinations revealed two well-circumscribed nodular masses localized in the wall of the left lateral ventricle and right temporal lobe, respectively. Both masses were completely resected, and the patient remains disease-free 2 years post-surgery. Histopathologically, the lesions were characterized by stratification. From outer to inner, there was a reactive glial component, lamellated well-differentiated muscle-like cells, densely compact collagen fibers and cellular tumor with nodular and hemangiopericytoma-like patterns, respectively. The myofibroblastic nature of this tumor was verified by immunohistochemical staining and ultrastructural analysis. Intraparenchymal myofibromatosis may be confused with, and should be distinguished from, meningioma, myopericytoma, solitary fibrous tumor, leiomyoma and inflammatory myofibroblastic tumor for accurate diagnosis and optimal treatment.
  • Stromal cells in the human gut show ultrastructural features of fibroblasts and smooth muscle cells but not myofibroblasts.

    Eyden, Brian P; Curry, Alan; Wang, Guofeng; Department of Histopathology, Christie NHS Foundation Trust, Manchester, United Kingdom. (2010-07-21)
    Abstract The free spindled cells of the lamina propria of the gut have been reported as showing fibroblastic, smooth-muscle and myofibroblastic differentiation. A precise understanding of the differentiation of these cells is essential for appreciating their functions, and this paper addresses this question using ultrastructural analysis. Histologically normal samples from different areas of the gastrointestinal tract were studied. Both subepithelial stromal cells, lying immediately beneath the basal lamina, and the deeper interstitial stromal cells, were studied. Subepithelial and interstitial cells had comparable features, reinforcing the idea that these formed a single reticulum of cells. Two major cell-types were identified. Some were smooth-muscle cells, on the basis of abundant myofilaments with focal densities, glycogen, an irregular cell surface, focal lamina and multiple attachment plaques alternating with plasmalemmal caveolae. Some cells had a lesser expression of these markers, especially of myofilaments, and were regarded as poorly differentiated smooth-muscle cells and descriptively referred to as 'myoid'. Other cells were fibroblastic to judge by prominent rough endoplasmic reticulum, an absence of myofilaments and lamina, but presence of focal adhesions. The fibronexus junctions of true myofibroblasts were not seen. The study emphasises that the smooth-muscle actin immunoreactivity in this anatomical site resides in smooth-muscle cells and not myofibroblasts, a view consistent with earlier ultrastructural and immunostaining results. The recognition that these cells are showing smooth-muscle or fibroblastic but not true myofibroblastic differentiation should inform our understanding of the function of these cells.
  • Diagnosis of alveolar rhabdomyosarcoma in effusion cytology: a diagnostic pitfall.

    Thiryayi, S A; Rana, D N; Roulson, J; Crosbie, P; Woodhead, M; Eyden, Brian P; Hasleton, Philip S; Manchester Cytology Centre, Manchester Royal Infirmary, Oxford Road, Manchester, UK. (2010-08)
  • Pleomorphic rhabdomyosarcoma showing smooth-muscle and fibrohistiocytic differentiation: a single case report.

    Eyden, Brian P; Department of Histopathology, The Christie NHS Foundation Trust, Manchester, United Kingdom. (2010-02)
    Rhabdomyosarcoma has traditionally been subclassified into alveolar, embryonal, and pleomorphic variants. Less commonly, spindle-cell, neuroendocrine, sclerosing, and lipid-rich or clear-cell subtypes are seen. The author recently encountered a myogenic sarcoma, with all the common markers of rhabdomyosarcoma, but expressing the unusual features of alpha-smooth-muscle actin and abundant rough endoplasmic reticulum (rER). This myogenic sarcoma, therefore, exhibited four lines of differentiation, and is documented here. The patient was a 65-year-old man with an inguinal soft tissue mass. Following surgical excision, the patient was given radiotherapy and was well without disease after 6 years. The tumor was positive for vimentin, desmin, alpha-smooth-muscle actin, alpha-sarcomeric actin, myogenin, MyoD1, and CD68. Cytoplasm was dominated by abundant rER intermingled with lipid droplets and lysosomes. Cell surfaces exhibited microvillous processes and focal adhesions, but no lamina. Subplasmalemmal smooth-muscle-type myofilaments with focal densities and rare sarcomeric filaments were seen. The low level of expression of some markers was interpreted as consistent with a poorly differentiated tumor. Given the four lines of differentiation--striated muscle, smooth muscle, fibroblastic, and histiocytic--a name reflecting its phenotype would be pleomorphic rhabdomyosarcoma showing smooth-muscle and fibrohistiocytic differentiation.
  • Spindle cell lesions of the bladder and urinary tract.

    Shanks, Jonathan H; Iczkowski, Kenneth A; Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK. (2009-11)
    Spindle cell lesions of the urinary tract encompass a variety of benign and malignant tumours as well as a group of lesions of controversial nomenclature that is the subject of ongoing debate. This review focuses on our current and evolving understanding of the lesion variably referred to as inflammatory myofibroblastic tumour, pseudosarcomatous myofibroblastic proliferation or inflammatory pseudotumour and the main differential diagnoses of sarcomatoid carcinoma and sarcoma. Other spindle cell lesions of the bladder are described.
  • Divergent differentiation in urothelial carcinoma and other bladder cancer subtypes with selected mimics.

    Shanks, Jonathan H; Iczkowski, Kenneth A; Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK. (2009-06)
    Conventional urothelial carcinoma accounts for most carcinomas of the urinary tract lining. However, neoplastic urothelium has the capacity to demonstrate enormous plasticity. A variety of unusual architectural patterns of urothelial carcinoma, such as the nested, microcystic and inverted variants, can be mistaken for reactive processes or benign tumours. Others such as the micropapillary, plasmacytoid and discohesive variants, can mimic metastatic tumour from other sites. The micropapillary variant in particular is more aggressive. In addition, urothelial carcinoma has a propensity to demonstrate divergent differentiation with glandular, squamous, small cell neuroendocrine, lymphoepithelioma-like, sarcomatoid or other elements. Pure squamous carcinoma or adenocarcinoma (the latter in particular) can be difficult to distinguish from contiguous or metastatic spread. Some variants have prognostic and potential therapeutic implications. Molecular genetic evidence has emerged recently supporting a close relationship between urothelial carcinoma and various divergent elements. Sarcomatoid carcinoma and its differential diagnosis with other spindle cell lesions of urinary tract will be covered in a separate review.
  • Oligosaccharides of hyaluronan induce angiogenesis through distinct CD44 and RHAMM-mediated signalling pathways involving Cdc2 and gamma-adducin.

    Matou-Nasri, S; Gaffney, J; Kumar, Shant; Slevin, M; School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester M1 5GD, UK. (2009-10)
    We used short-interfering RNA (siRNA) to knockdown the hyaluronan (HA) receptors CD44 and the receptor for hyaluronan-mediated motility (RHAMM) in vascular endothelial cells to investigate their role in angiogenesis. We showed that CD44 and RHAMM single knockdown inhibited low molecular weight hyaluronan (o-HA)-induced endothelial cell tube formation in Matrigel, but no change in the control, epidermal growth factor-induced tube formation was observed. Using a Kinexus phosphoprotein array and confirmational Western blotting we were able to show a differential effect on HA-induced protein expression after CD44 and RHAMM knockdown. CD44 knockdown abolished o-HA-induced membrane phospho-protein kinase C-alpha (PKC-alpha) and down-stream phospho-gamma-adducin expression. Using the PKC inhibitor Go6976, we demonstrated the involvement of PKC-alpha and gamma-adducin in o-HA-induced tube formation, whilst o-HA-induced enzymatic activity of MMP9 was also reduced. This suggests that endothelial tube formation involves activation of MMP9 via PKC-alpha. Furthermore, the involvement of gamma-adducin in o-HA-induced F-actin cytoskeleton rearrangement was CD44-dependent and the reduction of CD44 expression lead to a change in endothelial cell morphology. Both RHAMM and CD44 knockdown completely inhibited o-HA-induced Cdc2 (Cdk1) phosphorylation suggesting a possible involvement in cell cycle control. Although CD44 and RHAMM are both involved in o-HA-induced endothelial tube formation in Matrigel, they mediate distinct angiogenic signalling pathway and for the first time we demonstrated the specific involvement of gamma-adducin in CD44/o-HA-induced endothelial tube formation. The data presented here extend our understanding of key stages of the processes of o-HA-induced angiogenesis which may have relevance to tumour progression.
  • Basement-membrane-related peri-vascular matrices not organised as a basal lamina: distribution in malignant tumours and benign lesions.

    Eyden, Brian P; Yamazaki, Kazuto; Menasce, Lia P; Charchanti, A; Agnantis, N J; Department of Histopathology, Christie Hospital NHS Trust, Manchester, United Kingdom. (2000-10)
    Peri-vascular matrices having a finely textured granular substructure have been identified in 27 human lesions: these were mostly malignancies but included benign tumours and reactive processes. The matrices were defined as stromal components surrounding endothelium and pericytes, and lying between vessels and adjacent lesional cells. They were identified as having a finely textured, uniform and moderately dense substructure, and differed from a conventional basal lamina expected at these sites by the absence of the typical lamina densa/lamina lucida configuration. By light microscope immunohistochemistry, vessels stained positively for laminin and collagen IV, two of the main proteins characterising a conventional basal lamina. The present observations emphasise the following. 1) The proteins laminin and collagen IV can be found in peri-vascular locations which have a finely textured granular substructure, and which have clearly defined ultrastructural differences from a conventional basal lamina. 2) While conventional light microscope immunohistochemistry demonstrates the presence and cellular location of proteins, electron microscopy is helpful for giving information on their physical organisation. 3) Peri-vascular granular matrices have a widespread distribution in malignant tumours but also exist in benign tumours and reactive lesions. This paper briefly discusses the possible functions of these matrices as modulators of cell biological processes.

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