Small Basal Cell Research Articles

A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20mm), with a 12-month follow-up

A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20mm), with a 12-month follow-up

Rare and unusual histological variants of prostatic carcinoma: clinical significance

We review the clinicopathological features of the following unusual histological variants of prostatic carcinoma: small cell carcinoma, ductal adenocarcinoma, sarcomatoid (carcinosarcoma), basal cell, squamous cell and adenosquamous, and urothelial carcinoma. These variants are rare and account for 5-10% of carcinomas that originate in the prostate. Some develop from acinar adenocarcinoma after hormonal or radiation therapy. They are usually aggressive tumours that often present with secondary deposits. The outcome is generally poor. Only basal cell carcinoma is seen as a low-grade carcinoma.

5% 5-Fluorouracil Cream for the Treatment of Small Superficial Basal Cell Carcinoma: Efficacy, Tolerability, Cosmetic Outcome, and Patient Satisfaction

5% 5-Fluorouracil Cream for the Treatment of Small Superficial Basal Cell Carcinoma: Efficacy, Tolerability, Cosmetic Outcome, and Patient Satisfaction

Characterization of benign and malignant prostate epithelial Hoechst 33342 side populations

The prostate epithelial stem cell has been proposed as the primary origin of neoplastic change in prostate cancer. However, the isolation and characterization of unexpanded prostate epithelial stem cells have proven problematic. A prostate epithelial side population (SP) has been isolated utilizing a modified Hoechst 33342 dye efflux assay from both benign and malignant prostate tissue. CD45(-ve), integrin alpha2(+ve) Hoechst 33342 SP and NSP cells were isolated by FACS, immunophenotyped and functionally characterized in 3D culture. FACS analysis revealed a verapamil sensitive SP accounting for 0.93 +/- 0.12% and 0.57 +/- 0.11% of the total epithelial population from both benign and malignant prostates. The benign SP phenotype revealed a heterogeneous cell population consisting predominantly of small basal cells containing minimal cytoplasm. Conversely, the malignant SP was of undetermined acinar origin and with a complete loss of expression of the CDK2 inhibitor p21(WAF1/Cip1). In vitro androgen-enhanced 3D culture of the benign and malignant SP cells led to the production of spheroids which had acinus like morphology and expressed primitive and basal cell markers. Incorporation of the CD133 marker isolated a further SP sub-fraction accounting for 0.037 +/- 0.01% of epithelial cells. Our observations are consistent with the Hoechst 33342 dye efflux assay isolating a stem cell enriched population which can be further sub-fractionated by CD133 selection. Moreover, the loss of the CDK inhibitor in malignancy is consistent with the hypothesis that neoplastic change originates in the stem cell compartment.

Amniotic Membrane Transplantation Combined with Antiviral and Steroid Therapy for Herpes Necrotizing Stromal Keratitis

To evaluate therapeutic effect of multilayer amniotic membrane transplantation (AMT) in conjunction with antiviral and corticosteroid therapy on herpes necrotizing stromal keratitis. Retrospective interventional case series. Fifteen patients (15 eyes) with herpes necrotizing stromal keratitis, persistent corneal inflammation, and impending ulcer, despite topical and systemic antiviral treatment for over 2 weeks. Multilayer AMT was performed in the 15 eyes. Antiviral medications and appropriate corticosteroids were administered after surgery. Remodeling of amniotic membrane (AM) and growth of epithelial cells were detected by confocal microscopy. Visual acuity and corneal status (ulceration, edema, and opacification). Follow-up ranged from 7 to 13 months (mean +/- standard deviation, 8.9+/-1.8). Visual acuity improved by > or =2 lines in 14 eyes. Central corneal ulcers healed completely at 2.0+/-0.6 weeks, and paracentral ulcers at 2.1+/-0.6 weeks (t = 0.314, P = 0.759). Corneal stromal thickness was restored in eyes with central ulcers at 2.4+/-1.2 weeks and in those with paracentral ulcers at 2.6+/-0.7 weeks (t = 0.425, P = 0.678). Superficial epithelial cells, together with small basal epithelial cells, gradually migrated to the surface of AM on postoperative weeks 1 to 3. There were corneal nebulae in 11 eyes, corneal maculae in 3 eyes, and a corneal leukoma in 1 eye at the end of follow-up. No recrudescence occurred in any eye. Multilayer AMT combined with antiviral and corticosteroid therapy appears effective in treating herpes necrotizing stromal keratitis. It provides patients with marked scars and visual impairment an opportunity for subsequent keratoplasty by arresting the inflammatory response and reducing the graft bed diameter.

Giant Vascular Eccrine Spiradenoma: Report of a Case with Immunohistochemical Study

We report a rare case of giant vascular eccrine spiradenoma (GVES) which developed in 56-yr-old Korean woman. It is a rare variant of eccrine spiradenoma (ES), which might be mistaken for angiomatous lesions in view of its florid vascularity and hemorrhagic features. Histogenesis of GVES is not clearly elucidated although it is known that ES presumably originates in the eccrine glands. To clarify the histogenesis of GVES, immunohistochemical stainings using various monoclonal antibodies were also performed. The tumor was composed of three types of cells, namely pale epithelial cells, small basal cells, and myoepithelial cells. Therefore, we conclude that GVES originated from eccrine gland and mainly differentiates toward secretory portion of secretory coil.

Ultrastructure of sporodochium and conidium development in the anamorphic fungus Epicoccum nigrum

Scanning and transmission electron microscopy were used to examine sporodochium and conidium development in Epicoccum nigrum Link. Each sporodochium, a slightly raised mass of hyphae consisting of a pseudoparenchymous stroma covered with muriform conidia, arose from a group of loosely packed hyphae that formed on the agar surface. Conidiophores developed from the surface of the stroma. Each possessed a two-layered wall consisting of an inner electron transparent layer and an outer electron dense layer. Most conidiophores consisted of only two cells, the apical of which became swollen and gave rise to a solitary conidium initial in a holoblastic fashion. This initial enlarged and became divided into a smaller basal cell and a larger apical cell by a transverse septum. While the basal cell did not divide further, the apical cell became divided into numerous cells as the result of the formation of longitudinal and transverse septa. As a conidium matured the electron transparent inner layer of its wall thickened while the surface of its electron dense outer wall layer became transformed into small wart-like surface ornaments. Conidium secession was schizolytic and involved a transverse splitting of the septum separating the basal cell of a conidium from its conidiophore. The end of the basal cell and the tip of the conidiophore became rounded off during conidium secession.

Accuracy of Bread-Loafing for BCC Excision Margin Control

Fusiform excisions are often employed for resection of small facial basal cell carcinomas (BCCs). There is some uncertainty regarding the accuracy of the bread-loafing method (examination of serial, transverse crosssections) for assessing the surgical margins of such excisions. In this study from a Mohs surgery practice, to see if this approach would have detected the residual tumor, investigators simulated bread-loaf sectioning in 42 small (<1-cm), well-defined, primary, nonmorpheaform …

Novel enzymatic isolation of an entire viable human limbal epithelial sheet.

To develop a reproducible method of isolating an intact viable human limbal epithelial sheet. Human pigmented limbus was incubated at 4 degrees C for 18 hours in supplemental hormonal epithelial medium (SHEM) containing 50 mg/mL dispase II and 100 mM sorbitol. A loose limbal epithelial sheet was separated by a spatula. The remaining stroma was digested and subcultured. The viability of isolated cells was assessed. Isolated epithelial sheets and remaining stroma were subjected to immunostaining. Sheets 1.5 mm in length were cultured in SHEM on plastic until confluence, and cell extracts were subjected to Western blot analysis. Intact limbal epithelial sheets were consistently isolated. Pigmented palisades of Vogt revealed large superficial squamous cells and small basal cuboidal cells. No epithelial cells grew from the remaining stroma. Mean viability was 80.7% +/- 9.1%. The basal epithelium was negative to keratin 3 and connexin 43, but was scatter positive for p63. The epithelial sheet showed negative staining for laminin 5 and collagen VII, but interrupted linear basal staining for collagen IV. The remaining stroma showed negative staining for laminin 5, positive linear staining for collagen IV in the basement membrane, and diffuse staining for collagen VII in the superior stroma subjacent to the basement membrane. Western blot analysis revealed that cells originating from the limbal sheets expressed keratin 3 and p63. An intact limbal epithelial sheet can be consistently and reproducibly isolated and contains stem cell characteristics in the basal epithelium by degrading laminin 5 and part of collagen IV, and disassembling collagen VII.

Imiquimod to Treat Different Cancers of the Epidermis

BACKGROUND Topical immunomodulatory therapy with imiquimod has been recently used for the treatment of actinic keratoses, intraepithelial carcinoma, and small basal cell carcinoma (BCC) besides the licensed indication of extragenital warts (condyloma). METHODS We treated several patients with particular epidermal neoplasias such as squamous cell cancer (SCC) and basal cell cancer of sclerodermiform type three times per week for 4 to 12 weeks. RESULTS We report several novel aspects of the treatment of epidermal cancers with self-applied, nonpainful, immunomodulatory therapy. First, we treated—for the first time—two immunosuppressed renal transplant patients for invasive SCC with imiquimod. Interestingly, systemic immunosuppression did not adversely affect the response to therapy. Second, one patient with the high-risk and aggressive growth pattern of basal cell cancer (sclerodermiform histology) was cured from his disease at a particular location in the face, suggesting sufficient penetration despite scarring. No recurrence was detected in another patient who suffered from 29 BCCs until almost 2-years follow-up. Third, the treatment of actinic keratoses in the face is substantially shorter (in the order of 4 to 6 weeks) as opposed to other skin cancers. Immunomodulatory treatment with imiquimod led to the demarcation of in situ actinic keratosis lesions that could not be identified using the dermatologist's experience, probably because of the existence of exclusive alterations on the molecular level. CONCLUSION Several novel aspects of immunomodulatory treatment with imiquimod and new indications such as selected cases of sclerodermiform BCC and SCC have been described. The texture of the skin at various different body locations may explain the varying sensitivities to imiquimod when facial skin is compared with skin on the extremities.

Heterotrimeric G Proteins Regulate Daughter Cell Size Asymmetry in Drosophila Neuroblast Divisions

Cell division often generates unequally sized daughter cells by off-center cleavages, which are due to either displacement of mitotic spindles or their asymmetry. Drosophila neuroblasts predominantly use the latter mechanism to divide into a large apical neuroblast and a small basal ganglion mother cell (GMC), where the neural fate determinants segregate. Apically localized components regulate both the spindle asymmetry and the localization of the determinants. Here, we show that asymmetric spindle formation depends on signaling mediated by the Gβ subunit of heterotrimeric G proteins. Gβ13F distributes throughout the neuroblast cortex. Its lack induces a large symmetric spindle and causes division into nearly equal-sized cells with normal segregation of the determinants. In contrast, elevated Gβ13F activity generates a small spindle, suggesting that this factor suppresses spindle development. Depletion of the apical components also results in the formation of a small symmetric spindle at metaphase. Therefore, the apical components and Gβ13F affect the mitotic spindle shape oppositely. We propose that differential activation of Gβ signaling biases spindle development within neuroblasts and thereby causes asymmetric spindles. Furthermore, the multiple equal cleavages of Gβ mutant neuroblasts accompany neural defects; this finding suggests indispensable roles of eccentric division in assuring the stem cell properties of neuroblasts.

Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry.

Asymmetric cell division is important in generating cell diversity from bacteria to mammals. Drosophila melanogaster neuroblasts are a useful model system for investigating asymmetric cell division because they establish distinct apical-basal cortical domains, have an asymmetric mitotic spindle aligned along the apical-basal axis, and divide unequally to produce a large apical neuroblast and a small basal daughter cell (GMC). Here we show that Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl) tumour suppressor proteins regulate multiple aspects of neuroblast asymmetric cell division. Dlg/Scrib/Lgl proteins show apical cortical enrichment at prophase/metaphase, and then have a uniform cortical distribution. Mutants have defects in basal protein targeting, a reduced apical cortical domain and reduced apical spindle size. Defects in apical cell and spindle pole size result in symmetric or inverted neuroblast cell divisions. Inverted divisions correlate with the appearance of abnormally small neuroblasts and large GMCs, showing that neuroblast/GMC identity is more tightly linked to cortical determinants than cell size. We conclude that Dlg/Scrib/Lgl are important in regulating cortical polarity, cell size asymmetry and mitotic spindle asymmetry in Drosophila neuroblasts.

Cryosurgery: unapproved uses, dosages, or indications

Most dermatologists around the world carry out some aspects of cryosurgery as part of their dermatologic surgery practice. Typically, this will be limited to commoner forms of focal, benign, premalignant and malignant epidermal lesions, such as viral warts, keratoses, and small basal cell carcinomas. Cold “injury” could be used to destroy almost any pathology if used aggressively enough, but in clinical practice in comparison with other modalities of treatment, one has to grade cryosurgery in relation to its success, morbidity, failure, and recurrence rates. There are, strictly speaking, no “unapproved” indications for cryosurgery. Textbooks in the field1–3 show a large range of focal skin pathologies that are treatable by cryosurgery: if one is to use it to its limits and understand the multiplicity of potential indications, it is important to know the scientific basis of the freeze damage used in clinical practice.

Cochlear Transduction: From Models to Molecules and Back Again

The strides made over the last few years towards understanding many details of cochlear function still leave a number of issues unresolved. Integrating the information from molecular, genetic and, increasingly, genomic sources requires models that provide close matching between data and theory. For both theoretical and experimental reasons, the difficult area in cochlear physiology has been to understand how sensory transduction operates at the basal end of the mammalian cochlea. The identification of candidate motor proteins in outer hair cells (OHCs) draws attention to the question of whether we understand cochlear tuning. Nevertheless, the association of the cloned motor protein ‘prestin’ with an anion transporter superfamily provides clues about the molecular nature of the OHC motor in the basolateral membrane, the utilisation of chloride in hair cells and the long-term stability of small basal turn cochlear hair cells.

Adenoid basal carcinomas of the cervix:A unique morphological evolution with cell cycle correlates

Adenoid basal carcinoma (ABC) is a rare cervical carcinoma of postmenopausal women composed of small basal-type (basaloid) cells with focal endocervical (“adenoid”) differentiation. ABCs are associated with high-grade squamous intraepithelial lesions (HSIL) and contain integrated human papillomavirus type 16 DNA. However, ABCs have a favorable prognosis and do not metastasize. Five (5) ABCs were analyzed histologically for a marker distinguishing basal/squamous from columnar (adenoid) differentiation (p63) and cell cycle activity (Ki-67), and compared with 20 cervical (CC) carcinomas. In contrast to other CCs, ABCs contained 4 distinct components, including (1) a classic HSIL; (2) a limited invasive component with squamoid maturation, often with a discrete layer of peripheral basal cells; (3) outgrowth of small basal cells from either HSIL or squamoid areas; (4) focal endocervical (adenoid) differentiation. ABCs showed distinct differences in cell cycle activity relative to CCs. Ki-67 positivity was high in associated HSHs but remained high and concentrated in the suprabasal cells of the invasive squamoid component of ABC. Moreover, proliferative index was variable to sharply reduced in areas of basaloid and adenoid differentiation, in contrast to conventional CCs. ABC is a unique neoplasm, not only by its transition through multiple phenotypes during invasion, but also by a proliferative index that is high in more mature neoplastic cells during the infiltrative process and reduced with progressive basal differentiation. The precise mechanism underlying this unique process of tumor evolution is unclear. However, the postmenopausal status of these patients suggests that host factors related to aging may influence tumor evolution and morphology after HPV 16 infection.

Characterisation of a sperm coating auto-antigen reacting with antisperm antibodies of infertile males using monoclonal antibodies.

In a previous study a number of sperm-specific antigens were identified which reacted with antisperm antibodies from both infertile and vasovasostomised males. To investigate the localisation and distribution of these antigens and their role in male fertility, monoclonal antibodies were raised against them; immunoblotting techniques were used to select only those antibodies which competed with human antisperm antibodies for these human auto-antigens. One antibody, NW21, reacted with an 18 kDa auto-antigen present on epididymal sperm but absent from testicular sperm. Immunohistochemical studies showed that the antigen is produced in small basal cells between the columnar epithelium of the corpus epididymis, passes up into the tubule and then coats sperm passing along the epididymis. Sperm stored in the cauda epididymis and ductus deferens stain strongly for this sperm coating glycoprotein. The localisation of this antigen supports the suggestion that auto-immune infertility may represent a response to epididymal rather than testicular sperm. Monoclonal antibodies raised to unique and immunologically accessible sperm coating proteins, produced in the epididymis rather than in the testis, would seem to present an excellent theoretical solution to male contraception.

Keratinocyte Growth Factor Inhibits Cross-linked Envelope Formation and Nucleosomal Fragmentation in Cultured Human Keratinocytes

Keratinocyte growth factor (KGF) exhibits paracrine action on numerous epithelia, including skin. We have found that cultures of normal human keratinocytes must attain confluence before KGF promotes an increase in cell number relative to untreated controls. In postconfluent cultures, treatment with KGF promoted tight packing of keratinocytes with a small basal cell morphology. Based on these observations, we hypothesized that KGF increased cell number in postconfluent cultures by affecting the ability of normal keratinocytes to undergo terminal differentiation and/or programmed cell death. In support of this hypothesis, keratinocytes treated with KGF produced fewer cross-linked envelopes and exhibited reduced membrane-associated transglutaminase activity relative to cells treated with epidermal growth factor or untreated controls. We also found that nucleosomal fragmentation was reduced in postconfluent cultures of KGF-treated keratinocytes. Furthermore, KGF-treated keratinocytes were more resistant to suspension-induced nucleosomal fragmentation than control or epidermal growth factor-treated cultures. Therefore, it appears that KGF modulates aspects of keratinocyte terminal differentiation which share features with programmed cell death. We propose that stromally-derived KGF may act as a paracrine survival factor in skin and perhaps other renewal tissues.

Evolution and ultrastructure of the bovine spermatogonia precursor cell line

The spermatogonial stem cell line in prepubertal and adult bovine testis was studied by electron microscopy and protein gene product 9.5 immunohistochemistry. Three successive spermatogonia precursor cell configurations were observed. Small basal stem cells were found to possess a spherical shape and nuclei with two to three nucleoli. They were observed in prepubertal testes (25 and 30 weeks) and in low numbers during all the stages of the seminiferous epithelial cycle in the adult. Aggregated spermatogonia precursor cells are the dominating germ cell type in the 25-week-old and 30-week-old calf. In the adult seminiferous epithelium, they cause expansion of the basal tubular compartment as they form dense groups containing up to 15 cells. These groups are observed concomitantly with cycling A-spermatogonia and preleptotenes at the beginning of spermatocytogenesis. At the end of A-spermatogonia propagation, the aggregated spermatogonia precursor cells separate and intermingle with cycling A-spermatogonia. The spermatogonia precursor cells can later be found together with I-spermatogonia as members of an interconnected cellular network of medium-sized cells. When the I-spermatogonia divide to form the smaller B-spermatogonia, the precursor cells, which stay connected with the cycling spermatogonial population, pass through a growth phase. They can now be considered as committed spermatogonia precursor cells and are continuously being transformed into A1-spermatogonia to start a new round of spermatocytogenesis. Ultrastructurally, all members of the precursor cell line are similar. However, a number of features have been found to show a quantitative increase (endoplasmic reticulum, mitochondria) or to exhibit a rising degree of complexity (nucleolus) during the progression from basal stem cells to committed spermatogonia precursor cells.

Myocardial ischemia induced by topical use of 5-fluorouracil

An 85-year-old woman, with known stable angina pectoris, was prescribed 5-fluorouracil cream to treat a small basal cell carcinoma on the forehead. Half an hour after application the patient developed her typical ischemic pain which persisted for 2 hours. Rechallenge, during hospitalization, resulted in recurrence of symptoms that were effectively controlled with sublingual isosorbide dinitrate. Prophylactic therapy with nitroglycerin patch enabled further use of the 5-fluorouracil cream for the next month.

The main excretory duct (Stensen's) of the human parotid gland: a transmission and scanning electron microscope study.

The epithelial cells of the human parotid main excretory duct (Stensen) were studied by transmission (TEM) and scanning (SEM) electron microscopy through a variety of procedures that allowed the visualization of their three-dimensional microanatomy. Stensen's duct in humans is lined, in its distal portion, with a pseudostratified epithelium with tall principal cells and smaller basal cells, while the epithelium becomes progressively stratified cylindrically toward the oral stoma. Goblet cells are scattered among the other epithelial cells. The principal cells exhibit, on their lateral surfaces, numerous flattened laminar folds probably involved in transporting processes. A well-developed smooth endoplasmic reticulum intermingled with mitochondria occupies the cellular apices. Some vesicles are recognized on the cytoplasmic surfaces of the apical and lateral plasmalemma when cytoplasmic organelles are removed. All these features are interpreted as being involved in the process of endocytosis. In both TEM and SEM, the principal cells show a relevant number of irregular apical protrusions that may represent a kind of apocrine secretion. Thus, with regard to function, the human Stensen's duct seems to modify the composition of saliva by processes of resorption and secretion, the latter coming from goblet cells as well. The basal cells have a surface microanatomy completely different from that of principal cells. They exhibit, in fact, only sparse microvillosities and smooth areas on their lateral aspect, while their stromal surface is greatly augmented by irregular thin ramified processes. The role of basal cells is also discussed.