Internalization of constitutive desmogleins with the subsequent induction of desmoglein 2 in pemphigus lesions

Acantholytic blisters in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are caused by a dissociation of desmosomes mediated by autoantibodies against desmoglein (Dsg) 3 and Dsg 1, respectively. The blistering occurs at the suprabasilar level in PV and at the subcorneal level in PF, which corresponds to the distribution of target antigens in the epidermis: there is a more prominent expression of Dsg 1 in the upper layer, whereas Dsg 3 is more prominent in the lower layer. To elucidate the histogenesis of acantholysis, we studied the alterations of the desmosomal components and the expression pattern of Dsg isoforms in the lesional and perilesional epidermis of pemphigus patients. The results demonstrated an internalization of the desmosomes in the lower epidermis of PV, PF and pemphigus vegetans. A similar phenomenon was induced in monolayers of keratinocytes cultured with PV sera. However, little change was observed in E-cadherin expression until acantholysis became manifest. This internalization occurred prior to overt acantholysis, and was frequently associated with the induction of Dsg 2 expression in the basilar or lower layers of the epidermis. These findings indicate an alteration of Dsg isoform expression in subclinical pemphigus lesions, which might be related to the characteristic acantholytic patterns: the suprabasilar layer in PV and the upper epidermis in PF.     

Radial asymmetry in the topography of retinoblastoma Clues to the cell of origin

Retinoblastoma is a malignancy of the human developing retina. In situ as well as in vitro studies have attributed tumoral histogenesis either to a primitive retinoblast with neuronal and glial differentiation potentials, or to a photosensory progenitor cell. Here it is shown in vivo that the retinal topography of 457 retinoblastoma and retinoma foci is radially asymmetrical. Tumor density appears to mimic the horizontal visual streak characteristic of red/green cone cell distribution. Such a non-random distribution seems to invalidate the hypothesis of a primitive multipotential neuroblast as the unique source of retinoblastoma and may support the view that retinoblastoma evolves along the cone cell lineage.     

Spermatocytic seminoma: toward further understanding of pathogenesis

Human germ cell tumours comprise a heterogeneous group of neoplasms which, based on pathobiological, genetic and clinical characteristics, can be subdivided into different entities. One of these subgroups relates to the so-called spermatocytic seminomas, benign tumours only found in the testis, preferentially in elderly men. Various developmental models for this type of germ cell tumour have been proposed and it is clear that spermatocytic seminoma has a pathogenesis independent from that of seminoma. A recent study examining expression of spermatogonial markers shows that spermatocytic seminomas are a heterogeneous group of tumours, with a supposed difference in origin, ie the majority from A(pale) or B spermatogonia, and a minority from A(dark) spermatogonia. However, this does not exclude an earlier cell of origin, possibly explaining the unique properties of this type of human germ cell tumour, with various counterparts in animals.     

Cyclin D1 inactivation extends proliferation and alters histogenesis in the postnatal mouse retina

Background: The cell‐cycle regulator Cyclin D1 is expressed in embryonic retinal progenitor cells (RPCs) and regulates their cell‐cycle rate and neurogenic output. We report here that Cyclin D1 also has important functions in postnatal retinal histogenesis. Results: The initial production of Müller glia and bipolar cells was enhanced in Cyclin D1 knockout (Ccnd1^?/?) retinas. Despite a steeper than normal rate of depletion of the RPC population at embryonic ages, postnatal Ccnd1^?/? retinas exhibited an extended window of proliferation, neurogenesis, and gliogenesis. Cyclin D3, normally confined to Müller glia, was prematurely expressed in Ccnd1^?/? RPCs. However, Cyclin D3 did not compensate for Cyclin D1 in regulating cell‐cycle kinetics or neurogenic output. Conclusions: The data presented in this study along with our previous finding that Cyclin D2 was unable to completely compensate for the absence of Cyclin D1 indicate that Cyclin D1 regulates retinal histogenesis in ways not shared by the other D‐cyclins. Developmental Dynamics 241:941–952, 2012. © 2012 Wiley Periodicals, Inc.     

涎腺导管癌伴巨细胞瘤样改变1例

以巨细胞瘤(GCT)为主要特征的原发性涎腺导管癌(SDC)是极为罕见的相对新认识的尚未完全定义组织发生学的一种肿瘤。本文报道1例发生于腮腺的伴有GCT的SDC,并结合文献,探讨其临床特点、病理学改变及组织学起源。     

Molecular characterization of post‐transplant lymphoproliferative disorders of donor origin occurring in liver transplant recipients

Post‐transplant lymphoproliferative disorders (PTLDs) represent a frequent complication of solid organ transplantation. Although most PTLDs arise from recipient lymphoid cells, a considerable fraction of cases may arise from donor B‐cells. In an attempt to clarify the histogenesis and pathogenesis of PTLDs derived from donor B‐cells, monoclonal PTLDs occurring in liver transplant recipients were chosen as a model to compare donor (D‐PTLDs) versus recipient PTLDs (R‐PTLDs). The tumour panel included nine D‐PTLDs and six R‐PTLDs. D‐PTLDs were early‐onset, EBV‐infected lymphoproliferations classified as polymorphic PTLD (P‐PTLD; n = 7) or diffuse large B‐cell lymphoma (DLBCL; n = 2) with tumour localization confined to the hepatic hilum. All R‐PTLDs were late‐onset DLBCLs and showed extrahepatic localization. A BCL‐6^?/MUM1⁺/CD138^+/? phenotype, consistent with a post‐germinal centre (GC) stage of pre‐terminal B‐cell differentiation, was observed in all D‐PTLDs and in 2/6 R‐PTLDs, whereas a BCL6⁺/MUM1^?/CD138^? profile, reminiscent of GC B‐cells, was detected in 4/6 R‐PTLDs. The presence of somatic IGHV hypermutation was observed in 6/9 D‐PTLDs and in 4/6 R‐PTLDs, suggesting derivation from antigen‐experienced B‐cells. IGHV4‐39 was the IGHV gene most frequently encountered, being rearranged in 3/9 D‐PTLDs. Among IGHV‐mutated PTLDs, a mutational profile suggesting antigen stimulation and/or selection was observed in 4/6 D‐s and in 2/4 R‐PTLDs. The presence of ongoing IGHV mutations was detected in 2/4 D‐PTLDs. Aberrant SHM was detected in 10/15 (66.7%) PTLDs, including 6/9 D‐PTLDs and 4/6 R‐PTLDs. Our findings suggest that (i) D‐PTLDs show a clinical presentation distinct from R‐PTLDs; (ii) immunophenotypic and genetic features of D‐PTLDs are consistent with mature, GC‐experienced B‐cells; (iii) transformed donor‐derived B‐cells may experience antigen‐driven stimulation and selection, and may acquire genetic lesions during neoplastic expansion in the recipient environment; and (iv) EBV infection and expression of viral oncoproteins may be relevant in the pathogenesis of D‐PTLDs. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

肾脏黏液性管状和梭形细胞癌的临床病理学探讨

目的探讨肾脏黏液性管状和梭形细胞癌的临床病理学特征及诊断、鉴别诊断要点。方法对2例肾脏黏液性管状和梭形细胞癌进行临床病理学及免疫组织化学分析。结果2例肾脏黏液性管状和梭形细胞癌患者，临床症状无特异性。肿瘤与周嗣组织分界清楚。镜下肿瘤呈不规则管状结构伴黏液样间质，瘤细胞呈立方形或梭形，胞浆嗜酸，核呈低级别。无核分裂或少见，无病理性核分裂。免疫组化染色EMA、AE1／AE3、Vim均阳性表达，3413E12弱或灶区阳性，S-100、SMA、HMB45、CD15、CgA及SYN均阴性，NSE在1例中有弱的表达。结论肾脏黏液性管状和梭形细胞癌是极为罕见的，明确该肿瘤的组织起源及病理特征，对于诊断及鉴别诊断有重要意义。     

A Historical Review of Paraffin and its Development as an Embedding Medium

Abstract

This report concerns the occurrence of heterotopic mucosa (HM) of the stomach in the lower rectum of a 55 year old white man. The morphology of HM, on routine hematoxylin-eosin and luxol-fast blue stains was that of an uninflamed, well-preserved, normal fundic mucosa (FM). Warthin-Starry and Giemsa stains did not reveal the presence of Helicobacter pylori. The immunohistochemical neuroendocrine markers usuallv demonstrable in the FM (chromogranin A, somatostatin) were positive in the HM, whereas those nondemonstrable in the FM (gastrin, glucagon, and insulin) were negative in the HM. The routine morphology and the presence and absence of neuroendocrine markers in the HM similar to those in the FM support the contention that the histogenesis of HM is congenital. (The J Histotechnol 18:61, 1995)     

The histogenesis of appendiceal carcinoid tumours

Twenty-two appendiceal carcinoid tumours, comprising 10 classical carcinoids, six tubular carcinoids and six goblet cell carcinoids were examined by histochemistry and immunohistochemistry. All of the tumours showed evidence of neuroendocrine differentiation. Classical carcinoids were invariably intimately associated with S-100 protein positive cells, supporting an origin from sub-epithelial neuroendocrine cells. Both tubular and goblet cell carcinoids expressed cytoplasmic mucin and immunoglobulin A, and neither were associated with S-100 protein positive cells. These observations suggest that tubular and goblet cell carcinoids are derived from epithelial crypt stem cells.     

Initial uterine alterations caused by developmental exposure to tamoxifen

Neonatal treatment of rodents with the widely used antiestrogen tamoxifen causes endometrial cancer and reproductive tract lesions reminiscent of the diethylstilbestrol (DES) syndrome. To evaluate the initial alterations induced in the developing uterus by tamoxifen or DES, neonatal Sprague-Dawley rat pups received 100 μg of tamoxifen (Group 1), 1 μg of DES (Group 2), or vehicle (Group 3) subcutaneously on days 1 through 5, and their uteri were studied by light microscopy, 5-bromo-2′ deoxyuridine immunohistochemistry, and computer-based morphometry. At Postnatal Day 6, epithelial hypertrophy (184.3% and 237.9% of controls) and myometrial thickening (151.9% and 180.0%) accounted for the uterotrophic effects of tamoxifen and DES. Evidence of secretory activity in epithelial cells, reduction of the epithelial BrdU-labeling index to 18.1% (tamoxifen) and 41.1% (DES) of controls, premature endometrial and myometrial differentiation, and the presence of eosinophils in both treatment groups suggested that tamoxifen exerted a DES-like estrogenic action on the developing uterus. These findings indicate that immediate epithelial and stromal-myometrial uterine alterations are found at Postnatal Day 6 after neonatal tamoxifen treatment.