HMSA4, Against a Melanosomal Fraction of Human Malignant Melanoma'

Total Page:16

File Type:pdf, Size:1020Kb

HMSA4, Against a Melanosomal Fraction of Human Malignant Melanoma' (CANCER RESEARCH 46, 2904-291 1, June l986J Development and Characterization of a Mouse Monoclonal Antibody, MoAb HMSA4, against a Melanosomal Fraction of Human Malignant Melanoma' Yutaka Akutsu and Kowichi Jimbow2 Department ofDermatology, Sappom Medical College, Sapporo, Japan ABSTRACF the rough ER of melanoma cells but not in melanosomes(18). In other recent studies (19), the antigen identified by MoAb To characterize the biologicalproperty unique to melanocytesand to NKI/C-3 was shown to be localized in the cytoplasm of mela utilize this property to establish laboratory diagnostic tools for malignant noma cells and concentrated in vacuoles and sometimes on melanoma, monoclonal antibody (MoAb) human melanosoine-associated antigen-l (HMSA-1), a mouse monoclonal antibody, was developed melanosomes. This study reports the development of MoAb against purified melanosomal fractions of human melanoma. MoAb HMSA-l by using isolated and solubilized melanosomal frac HMSA-1 belongsto an IgG1 (tc)subclass.Fractionationofcell organelles tions of human melanoma and describesthe specificity and the combined with enzyme linked immunosorbent assay analysis indicated distribution of antigen(s) reactive with it in normal and patho that the antigen(s) reactive with MoAb HMSA-1 is localized in mela logical tissues. The purity of melanosomal fraction was ana nosome and endoplasmic reticulum fractions and that it Is related to lyzed by enzyme markers of cytoplasmic organelles and by melanosomal protein and its precursor forms. The localization of the electron microscopy (20, 21). antigen In the melanosome and endoplasmic reticulum was also confirmed by immunoelectronmicroscopy.Characteristically, MoAb HMSA-1 re acted with formalin-fixed and paraffin-processed tissues of melanocytic MATERIALS AND METHODS nevi and malignant melanoma, including amelanotic lesions. It did not react with normal melanocytes, normal tissues and organs from fetuses Preparation ofMelanosomal Fraction from Human Melanoma Thsue. and adults, or most non-melanocytic tumors. Thus MoAb HMSA-I Human melanoma tissue was obtained from fresh autopsy melanoma identifies the differentiation antigen for the melanosome-associated prop tissues of liver and lung and was processed to isolate melanosomal erty in neoplastic melanocytes and is a useful adjunct for immunohisto fractions by our previously describedmethod (3, 18, 20, 22). In brief, logical diagnosis of melanocytic lesions on routine paraffin sections. melanoma tissue was minced with a 0.25 M sucrose-4 mM phosphate @ buffer, pH 6.8 (2 ml/g oftumor), to which 10 phenylmethylsulfonyl fluoride prepared in isopropyl alcohol was added to avoid proteolytic INTRODUCI1ON digestion. Then it was homogenized with a tissue grinder (Nihon Seiki Synthesis of melanosomes is a unique biological property in Co., Ltd., Tokyo, Japan) at 1000 rpm for 3 mm. Nuclear and cell fragments were sedimented by layering the homogenates on 0.5 M normal and malignant melanocytes. Melanosomes are mem sucrose and spinning them at 500 rpm for 10 mm. The crude melano brane-delimited organelles and are composed of the melanin somal fraction was then purified by a discontinuous sucrose density forming enzyme tyrosinase, structural matrix proteins, melanin, gradient ultracentrifugation (1.0—2.0 M sucrose) at 105,000 x g for 2 h and lipids (1—3).Themelanocytes which in many genetic dis with a Hitachi RPS-25S rotor. Next, the melanosomal fraction was orders exhibit abnormal melanin pigmentation synthesize mel suspended in 0.1% Brij 35 and 0.5% sodium deoxycholate in 4 nmi anosomes that are disoriented in their matrix or that are cx phosphate buffer, pH 6.8, at a concentration of about 15 mg of protein tremely large or associated with a peculiar substructure (4, 5). per ml, stirred with a Polytron homogenizer(Kinematica,Luzern, The melanosomes in malignant melanoma and certain forms Switzerland gauge 5), and centrifuged (105,000 x g, 30 mm). The of pigmented melanocytic nevi also become markedly aberrant supernatant was collected, applied to a DE52 column, and eluted with in their matrix substructures as well as in their manner of 0.25 MKCI in 4 mMphosphate buffer, pH 6.8. Immunization. Four 3-month-old BALB/c mice were immunized with organization (6—9). the melanosomal fraction of human malignant melanoma For the The development of MoAb3 to form cell components has initial immunization, 2.0 mg of melanosomal protein in 0.5 ml of provided specific tools for elucidating the molecular nature of phosphate buffer was injected s.c. with Freund's complete adjuvant. the antigenic properties of the cells (10). Antigenic determi After a 2-week rest, the mice were boosted s.c. 3 times with the same nants with unique biological properties defined by MoAb have amount of melanosomal protein in Freund's incomplete adjuvant. A been utilized for characterization of tumor-associated products test bleed was carried out through the eyes after the third boost. and in immunohistopathological and even therapeutic ap Hybridomas Secreting Antibodies. Three days after the last boost proachesto malignant melanoma (11—15).Most ofthese MoAb with an i.p. injection ofthe solubilized melanosomal fraction, the spleen have been directed against surface antigen(s) on the melanoma was aseptically removed, and splenocyteswere dissociated with scissors cells. Occasionally, however, MoAb which identify the cyto and a syringe to make a single cell suspension. Splenocytes (1 x 10 cells)werethenfusedwith the non-secretingmyelomacellsof Sp2/O- plasmic components have also been developed (16, 17). We Ag14 (6 x 10' cells) in the presence of44.6% polyethylene glycol 4000 have shown recently that MoAb 465.12, which belongs to the and 10.7% dimethyl sulfoxide in RPMI 1640 medium (10, 23). The latter category of MoAb, identifies antigen protein localized in resultant cells were suspendedin hypoxanthine, aminopterin, and thy midine in RPMI 1640 and 10% fetal calf serum with 1 nmi non Received 9/5/85; revised 12/30/85; accepted 2/18/86. The costs of publication of this article were defrayedin part by the payment essential amino acid supplemented with 1 mr@i sodium pyruvate and of page charges. This article must therefore be hereby marked advertisementin antibiotics and distributed in the 240 wells (1 mI/well) of multi-well accordancewith 18 U.S.C. Section 1734solelyto indicatethis fact. plates (Flow Laboratories, Inc., McLean, VA). Subsequently, selected i This study was supported by Grants-in-Md for Cancer Research, Nos. 59010027,60015083,and 6048250 from the MinistryofEducation, Scienceand hybridomas were expanded in hypoxanthine-thymidine medium (hy Culture and Nos. 60-9 from Ministry ofWelfare, and by the Aifred-Marchionini poxanthine-aminopterin-thymidine medium from which aminopterin Foundation. was omitted). The supernatants ofwells with clones were collected and 2 To whom requests for reprints should be addressed. tested for antibody activity. Hybridomas secreting antibodies were 3The abbreviationsusedare: MoAb,monoclonalantibody(-lea);HMSA-l, humanmelanosome-associatedantigen-1;ELISA,enzymelinkedimmunosorbent subcloned 3 times by a limiting dilution in the presence of murine assay;ER, endoplasmicreticulum;PBS, phosphate bufferedsaline;SDS-PAGE, splenocytes as feeder cells. Ascitic fluid was obtained 2 to 3 weeks after sodiumdodecylsulfate-polyacrylamidegelelectrophoresis. injection of hybridoma cells (5 x l0@cells)secreting antibody into the 2904 Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1986 American Association for Cancer Research. MoAb HMSA-1 peritoneal cavity of BALB/c mice primed 1 week earlier with 0.5 ml of natant supplemented with 0.02% saponin) for 30 min at room temper pristane. Spent culture media and ascitic fluid were used as the sources ature. They were then incubated with biotinylated horse anti-mouse of antibody. IgG and avidin:biotin:peroxidase complex (Vector Laboratories Burlin Enzyme Linked Immunosorbent Assay. Antibodies were tested for game,CA) for 30 mm eachat room temperature. After a DAB reaction, binding to the solubilized melanosome preparation ofhuman malignant the cells were postfixed with 1% 0s04-cacodylate buffer (0.1 M, pH melanoma by the ELISA described in our previous report with minor 7.2) solution, dehydrated, and embedded in epon 812. Thin sections modifications (18). Fifty Ml of the solubilized melanosomal protein of were made by a Porter Blum MT-2 microtome and observed with a human malignant melanoma or cellular blue nevi were layered into the Hitachi HS-8 electron microscope without counterstaining. wells of a microtiter plate (Dynatech Laboratories, Sussex, U. K.), and the plate was left standing for 2 h at room temperature. The isolation and solubilization of the melanosomal fraction from human cellular RESULTh blueneviwascarriedout with thesamemethodusedmelanomatissue. The wellswerecoatedwith 2% ovalbuminsolution containing0.1% Purified Melanosome Fraction as an Antigen Source. Approx sodium azide for 45 mm and washed 5 times with PBS. The solubiized imately 20 species of polypeptide bands were discerned in the melanosomal fraction was incubated with 50 @tlofspent culture media melanosomal fraction used for immunization under SDS for 2 h at room temperature. After washing 3 times with PBS, 50 g@lof PAGE. Their sizesrangedfrom 10,000 to 150,000 daltons,and peroxidase-labeled rabbit anti-mouse IgG (1/5000 diluted; Dako Im one of them, approximately 70,000 daltons in size, corre munochemical, Inc., Tokyo, Japan) were added to
Recommended publications
  • Metastasizing Melanoma Formation Caused by Expression of Activated N-Rasq61k on an Ink4a-Deficient Background
    Research Article Metastasizing Melanoma Formation Caused by Expression of Activated N-RasQ61K on an INK4a-Deficient Background Julien Ackermann,1 Manon Frutschi,1 Kostas Kaloulis,1 Thomas McKee,2 Andreas Trumpp,1 and Friedrich Beermann1 1ISREC, Swiss Institute for Experimental Cancer Research, National Center of Competence in Research Molecular Oncology, Epalinges, Switzerland and 2Institute of Pathology, University of Lausanne, Lausanne, Switzerland Abstract the most common factors predisposing to melanoma formation in humans is the INK4a/ARF locus (4), which is inactivated with high In human cutaneous malignant melanoma, a predominance of frequency in human melanoma. This locus encodes two distinct activated mutations in the N-ras gene has been documented. INK4a ARF ARF To obtain a mouse model most closely mimicking the human proteins by alternative exon usage, p16 and p14 (p19 in disease, a transgenic mouse line was generated by targeting mice), which function as tumor suppressor genes in the pRB and expression of dominant-active human N-ras (N-RasQ61K) to the p53 pathways, respectively (4, 5). Gene-targeted mice, where p16INK4a and p19ARF are deleted, develop a large variety of tumors melanocyte lineage by tyrosinase regulatory sequences INK4a Q61K but fail to develop melanoma (6). Mice deficient in p16 but (Tyr::N-Ras ). Transgenic mice show hyperpigmented skin ARF and develop cutaneous metastasizing melanoma. Consistent which retain one copy of p19 show carcinogen-induced with the tumor suppressor function of the INK4a locus that susceptibility to metastatic melanoma (7, 8). Transgenic mice that encodes p16INK4A and p19ARF, >90% of Tyr::N-RasQ61K INK4aÀ/À express a mutant form of H-ras specifically in melanocytes showed melanocytic hyperplasia with intense skin pigmentation (9), which transgenic mice develop melanoma at 6 months.
    [Show full text]
  • Laser Treatment for Pigmentation
    Laser treatment for pigmentation Sunspots and freckles In lesions such as solar lentigines (sun induced age spots), lentigo simplex and ephelides (freckles) the pigment (melanin) is in the top layers of the skin. Many lasers that selectively target melanin or simply remove the top layers will lead to improvement. One to two treatments will be necessary. There are many non-laser treatment approaches to treat such spots. However, if laser therapy is chosen, there are many different types of laser that can be used including Q-switched lasers [Q switched (QS) alexandrite, QS ruby (694nm)], long-pulsed, fractionated thulium (1927nm) and ablative lasers. IPL (filter 500-600nm) can also be very effective. However, it is common to see the pigmentation return over time. Treatments need to be avoided if the skin is tanned because this greatly increases the risk of complications. Seborrhoeic warts and dermatosis papulosa nigra Some conditions that present as dark spots are in fact wart-like and sit on the surface of the skin such as seborhoeic keratoses and dermatosis papulosa nigra and epidermal naevi. These conditions require physical removal. This is most commonly treated with a curette if thick or with fine wire diathermy particularly for the dermatosis papulosa nigra. Ablative lasers may also be used including CO2 in combination with a curette or an erbium YAG laser which reliably gives the best results. These lesions have a tendency to return over a number of years and maintenance treatments may be needed. Pigmented birth marks – Becker’s naevus Current lasers are unable to remove pigmented birthmarks without scarring.
    [Show full text]
  • Dermatopathology
    Dermatopathology Clay Cockerell • Martin C. Mihm Jr. • Brian J. Hall Cary Chisholm • Chad Jessup • Margaret Merola With contributions from: Jerad M. Gardner • Talley Whang Dermatopathology Clinicopathological Correlations Clay Cockerell Cary Chisholm Department of Dermatology Department of Pathology and Dermatopathology University of Texas Southwestern Medical Center Central Texas Pathology Laboratory Dallas , TX Waco , TX USA USA Martin C. Mihm Jr. Chad Jessup Department of Dermatology Department of Dermatology Brigham and Women’s Hospital Tufts Medical Center Boston , MA Boston , MA USA USA Brian J. Hall Margaret Merola Department of Dermatology Department of Pathology University of Texas Southwestern Medical Center Brigham and Women’s Hospital Dallas , TX Boston , MA USA USA With contributions from: Jerad M. Gardner Talley Whang Department of Pathology and Dermatology Harvard Vanguard Medical Associates University of Arkansas for Medical Sciences Boston, MA Little Rock, AR USA USA ISBN 978-1-4471-5447-1 ISBN 978-1-4471-5448-8 (eBook) DOI 10.1007/978-1-4471-5448-8 Springer London Heidelberg New York Dordrecht Library of Congress Control Number: 2013956345 © Springer-Verlag London 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.
    [Show full text]
  • Hyperpigmented Patches on a Woman's Sun-Exposed Face
    What’s Your Diagnosis?® Hyperpigmented Patches on a Woman’s Sun-Exposed Face: What’s the Cause? Alexander K. C. Leung, MD, and Benjamin Barankin, MD 45-year-old woman presented with brownish macules and Her past health was unremarkable, and she was not on any patches on her face. The pigmentation had developed ap- topical or oral medications. She denied any history of inflam- A proximately 10 years ago with the birth of her third child. matory dermatosis prior to the appearance of her skin problem. The lesions had gradually increased in size and number over The family history was not contributory. time. She had taken oral contraceptives for a few years after the Physical examination revealed symmetric, well-circumscribed, birth of her second child. She enjoyed a variety of outdoor ac- brownish macules and patches with irregular borders on the tivities, and she reported that the pigmentation was more pro- forehead, cheeks, nose, upper lip, and chin. The rest of the nounced with sun exposure. physical examination findings were normal. What’s Your Diagnosis? A. Solar lentigo D. Melasma B. Ephelides (freckles) E. Café au lait macules C. Actinic dyschromia www.consultant360.com • August 2017 • CONSULTANT 485 What’s Your Diagnosis?® Answer: Melasma A diagnosis of melasma was made. Wood lamp examination basement membrane disruption and dermal changes, indepen- showed accentuation of pigmentation suggestive of epidermal dent of UV radiation.1,17 pigmentation. The patient was treated with a series of trichlo- roacetic acid chemical peels, as well as a topical azelaic acid and HISTOPATHOLOGY a retinoid-hydroquinone-steroid (modified Kligman) formula- Three histologic patterns of pigmentation have been described: tion with significant, albeit incomplete, improvement.
    [Show full text]
  • Quality of Life and Photodermatoses in People with Albinism in Benin City Nigeria
    QUALITY OF LIFE AND PHOTODERMATOSES IN PEOPLE WITH ALBINISM IN BENIN CITY NIGERIA DISSERTATION SUBMITTED TO NATIONAL POSTGRADUATE MEDICAL COLLEGE OF NIGERIA IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE FELLOWSHIP IN INTERNAL MEDICINE (SUB-SPECIALTY: DERMATOLOGY) BY DR CYNTHIA ROLI MADUBUKO MB,BS (BENIN) DEPARTMENT OF MEDICINE UNIVERSITY OF BENIN TEACHING HOSPITAL, BENIN CITY, EDO STATE, NIGERIA NOVEMBER, 2016. i DECLARATION I hereby declare that this work is original and no part of it has been presented to any other college for a fellowship dissertation nor has it been submitted elsewhere for publication. Signature.................................... Date........................... Dr. Cynthia Roli Madubuko ii SUPERVISION We the undersigned have supervised the writing of this dissertation and the execution of this study. SIGNATURE: …………………………………… DATE: …………………………………………… YEAR OF FELLOWSHIP: ……………………… DR. B. OKWARA MBBS, FMCP Consultant Physician/ Dermatologist and Venereologist Department of Internal Medicine, University of Benin Teaching Hospital, Benin City, Nigeria. SIGNATURE: …………………………………… DATE: …………………………………………… YEAR OF FELLOWSHIP: ……………………… PROF. A.N. ONUNU MBBS, FWACP, FACP Consultant Physician/ Dermatologist and Venereologist Department of Internal Medicine, University of Benin Teaching Hospital, Benin City, Nigeria. SIGNATURE: …………………………………… DATE: …………………………………………… YEAR OF FELLOWSHIP: ……………………… PROF. E.P KUBEYINJE MBBS, FRCP (London), FWACP Consultant Physician Dermatologist and Venereologist Department of Internal Medicine, University of Benin Teaching Hospital, Benin City, Nigeria. iii CERTIFICATION I certify that this is a part 2 dissertation of the National postgraduate Medical College of Nigeria by Dr. Cynthia Roli Madubuko, of the Department of Internal Medicine, University of Benin Teaching Hospital, Benin City, under the supervision of Prof. A.N Onunu, Prof. E.P. Kubeyinje and Dr. B. Okwara Sign……………………………………. Date.............................................. DR OMUEMU, MBBS, FWACP.
    [Show full text]
  • Dermamelan ® Treatment for Melasma and Hyperpigmentation
    Dermamelan ® treatment for melasma and hyperpigmentation Jean Luc Levy Expert Laser, Dermatologist Lausanne, Switzerland [email protected] Incidence of Melasma Caucasian Melasma is estimated to occur in 50%-70% of pregnancies among US women, usually during the 2nd or 3rd trimester of pregnancy. Asian In Asian countries, the estimated prevalence of melasma within skin type III-V is estimated to be as high as 40% in females and 20% in males. Hispanic Among Mexican women, the incidence is estimated to be about 80%, with more than one-third of these patients having the disease for life. Retrospective Study on the Clinical Presentation and Treatment Outcome of Melasma in a Tertiary Dermatolofical Referral Centre in Singapore C L Goh, C N Dlova, Singapore Med J 1999; Vol 40(07): Melasma in Orientals. Sivayathorn A. Clin Drug Invest 1995; 10 (Suppl 2):24-40. ‘Utilizing combination therapy to optimize melasma outcomes’, M, I, Rendon(2004), Journal of Drugs in Dermatology, Sept-Oct. Facial melasma : Sun history Majority of melasma are very sensitive to sun exposure and tanned during summer - Sunblock regurlaly applied are poorly effective - During winter quality of life is better Some of them are poorly sensitive to sun exposure and colour acquired is near from the surrounding skin - During winter color differences between melasma and surrounding skin is high and covermark required Upper forehead without due to the tissue Sun exposed and non sun exposed areas Facial melasma : locations Forehead : with commonly a lighten aspect if hair is used
    [Show full text]
  • Q-Switched 1064/532 Nm Laser with Picosecond Pulse to Treat Benign Hyperpigmentations: a Single-Center Retrospective Study
    applied sciences Article Q-Switched 1064/532 nm Laser with Picosecond Pulse to Treat Benign Hyperpigmentations: A Single-Center Retrospective Study Martina Silvestri 1,2, Luigi Bennardo 1,3 , Elena Zappia 1, Federica Tamburi 1, Norma Cameli 2, Giovanni Cannarozzo 4,* and Steven Paul Nisticò 1 1 Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy; [email protected] (M.S.); [email protected] (L.B.); [email protected] (E.Z.); [email protected] (F.T.); [email protected] (S.P.N.) 2 San Gallicano Dermatological Institute, IRCCS, 00100 Rome, Italy; [email protected] 3 Unit of Dermatology, Mariano Santo Hospital, 87100 Cosenza, Italy 4 Unit of Dermatology, Tor Vergata University, 00100 Rome, Italy * Correspondence: [email protected]; Tel.: +39-09613647195 Abstract: (1) Benign melanoses are a frequent issue in aesthetic dermatology. Solar lentigo, ephelides, café au lait spots, and other melanoses represent a cosmetic issue for a growing number of subjects. The Q-switched 1064/532-nanometer (nm) laser may be considered the gold standard for manage- ment of these aesthetic issues. A new generation of Q-switched lasers, capable of concentrating the energy pulse in the spectrum of hundreds of picoseconds, is emerging, promising better results than previous ones. In this paper, we report the use of a Q-switched laser with a picosecond pulse to Citation: Silvestri, M.; Bennardo, L.; manage hypermelanoses. (2) Methods: 36 patients seeking melanosis removal were retrospectively Zappia, E.; Tamburi, F.; Cameli, N.; enrolled at Magna Graecia University of Catanzaro. Treatment parameters, although variable, were Cannarozzo, G.; Nisticò, S.P.
    [Show full text]
  • Pediatric Dermatology- Pigmented Lesions
    Pediatric Dermatology- Pigmented Lesions OPTI-West/Western University of Health Sciences- Silver Falls Dermatology Presenters: Bryce Lynn Desmond, DO; Ben Perry, DO Contributions from: Lauren Boudreaux, DO; Stephanie Howerter, DO; Collin Blattner, DO; Karsten Johnson, DO Disclosures • We have no financial or conflicts of interest to report Melanocyte Basic Science • Neural crest origin • Migrate to epidermis, dermis, leptomeninges, retina, choroid, iris, mucous membrane epithelium, inner ear, cochlea, vestibular system • Embryology • First appearance at the end of the 1st trimester • Able to synthesize melanin at the beginning of the 2nd trimester • Ratio of melanocytes to basal cells is 1:10 in skin and 1:4 in hair • Equal numbers of melanocytes across different races • Type, number, size, dispersion, and degree of melanization of the melanosomes determines pigmentation Nevus of Ota • A.k.a. Nevus Fuscocoeruleus Ophthalmomaxillaris • Onset at birth (50-60%) or 2nd decade • Larger than mongolian spot, does not typically regress spontaneously • Often first 2 branches of trigeminal nerve • Other involved sites include ipsilateral sclera (~66%), tympanum (55%), nasal mucosa (30%). • ~50 cases of melanoma reported • Reported rates of malignant transformation, 0.5%-25% in Asian populations • Ocular melanoma of choroid, orbit, chiasma, meninges have been observed in patients with clinical ocular hyperpigmentation. • Acquired variation seen in primarily Chinese or Japanese adults is called Hori’s nevus • Tx: Q-switched ruby, alexandrite, and
    [Show full text]
  • Partial Unilateral Lentiginoses
    igmentar f P y D l o i a so n r r d u e de Lima Grynszpan et al., Pigmentary Disorders 2015, 2:4 r o J s Journal of Pigmentary Disorders DOI: 10.4172/2376-0427.1000175 ISSN: 2376-0427 Case Report Open Access Partial Unilateral Lentiginoses Rachel de Lima Grynszpan1, Joao Paulo Niemeyer Corbellini2, Beatriz Maria Gaiser1 and Marcia Ramos-e-Silva3* 1Dermatologist and Former Post-Graduation Student – Sector of Dermatology and Post-Graduation Course, HUCFF-UFRJ and School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil 2Dermatologist and Supervisor of the General Dermatology and Photodermatology Out-Patient Clinics – Sector of Dermatology and Post-Graduation Course, HUCFF- UFRJ and School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil 3Associate Professor and Chair – Sector of Dermatology and Post-Graduation Course, HUCFF-UFRJ, and School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Abstract The authors present a case of a rare pigmentation disorder, partial unilateral lentiginosis (PUL), which is characterized by multiple lentigines located in only one side of the body with histopathology of lentigine. Keywords: Lentigines; Partial unilateral lentiginosis; Pigmentation At dermatologic examination, small brownish macules were observed on the back of the right hand, right cervical region, right Introduction upper chest, right lower lip and right forehead up to the medial line, Partial unilateral lentiginosis (PUL) is a rare pigmentation disorder characterized by multiple lentigines located in only one side of the body, which histopathologically show typical finding of lentigine [1,2]. It is characterized by small, well delimited, hyperchromic macules, distributed in a limited area of the body, which can affect one or more dermatomes and stop at the median line.
    [Show full text]
  • Clinical Pigmented Skin Lesions Nontest-June 11
    Recognizing Melanocytic Lesions James E. Fitzpatrick, M.D. University of Colorado Health Sciences Center No conflicts of interest to report Pigmented Skin Lesions L Pigmented keratinocyte neoplasias – Solar lentigo – Seborrheic keratosis – Pigmented actinic keratosis (uncommon) L Melanocytic hyperactivity – Ephelides (freckles) – Café-au-lait macules L Melanocytic neoplasia – Simple lentigo (lentigo simplex) – Benign nevocellular nevi – Dermal melanocytoses – Atypical (dysplastic) nevus – Malignant melanocytic lesions Solar Lentigo (Lentigo Senilis, Lentigo Solaris, Liver Spot, Age Spot) L Proliferation of keratinocytes with ↑ melanin – Variable hyperplasia in number of melanocytes L Pathogenesis- ultraviolet light damage Note associated solar purpura Solar Lentigo L Older patients L Light skin type L Photodistributed L Benign course L Problem- distinguishing form lentigo maligna Seborrheic Keratosis “Barnacles of Aging” L Epithelial proliferation L Common- 89% of geriatric population L Pathogenesis unknown – Follicular tumor (best evidence) – FGFR3 mutations in a subset Seborrheic Keratosis Clinical Features L Distribution- trunk>head and neck>extremities L Primary lesion – Exophytic papule with velvety to verrucous surface- “stuck on appearance” – Color- white, gray, tan, brown, black L Complications- inflammation, pruritus, and simulation of cutaneous malignancy L Malignancy potential- none to low (BCC?) Seborrheic Keratosis Seborrheic Keratosis- skin tag-like variant Pigmented Seborrheic Keratosis Inflamed Seborrheic Keratosis Café-au-Lait
    [Show full text]
  • Lentigo Simplex= النمشة البسيطة
    اﻠﺒﺴﻴﻄﺔ اﻠﻨﻤﺸﺔ =Lentigo simplex LENTIGO SIMPLEX Epidemiology The frequency of lentigo simplex in children and adults has not been determined. There does not appear to be a racial or gender predilection. Lentigo simplex is the most common histopathologic pattern of darkly pigmented lesions excised from acral sites of darkly pigmented races. Pigmented nail bands, noted in up to 20 percent of Japanese, may have histopathologic features of lentigo simplex. For agminated lentigines, the population prevalence is unknown, but it is believed to be rare. 1 / 8 اﻠﺒﺴﻴﻄﺔ اﻠﻨﻤﺸﺔ =Lentigo simplex Etiology and Pathogenesis The increased density of melanocytes in lentigines is presumably due to an underlying developmental or intrinsic defect in melanocyte homeostasis. In some lentigines, the presence of melanin macroglobules in melanocytes and keratinocytes suggests that defects affecting melanization pathways are also involved. The presence of lentigo simplex in association with somatic abnormalities in such diverse conditions as Peutz-Jeghers syndrome, LEPOARD syndrome (lentigines; electrocardiogram conduction defects; ocular hypertelorism; pulmonary stenosis; abnormalities of genitalia; retardation of growth, and sensorineural deafness), and LAMB/myxoma syndrome suggests that lentigo development may be influenced by a number of different genetic factors. For agminated lentigines, it is possible that chromosomal mosaicism plays a role in the development of the localized collection of lentigines. Clinical Findings HISTORY Unlike solar lentigines, lentigo simplex is thought to be largely UVR independent. Lentigo simplex may appear as early as the first decade and may occur anywhere on skin or mucous membranes. Generalized lentigines may occur as an isolated phenomenon without known familial aggregation and first appear at birth, during infancy, or during adulthood.
    [Show full text]
  • Photoageing Skin of the Elderly
    Malaysian Family Physician 2010; Volume 5, Number 1 ISSN: 1985-207X (print), 1985-2274 (electronic) ©Academy of Family Physicians of Malaysia Online version: http://www.e-mfp.org/ CME Article PHOTOAGEING SKIN OF THE ELDERLY SB Khoo FRACGP, Penang Medical College Address for correspondence: Dr Khoo Siew Beng, Senior Lecturer & Family Physician, Penang Medical College, No 4, Sepoy Lines Road, 10450 Penang, Malaysia. Tel: 604-2263 459, Email: [email protected] Khoo SB. Photoageing skin of the elderly. Malaysian Family Physician. 2010;5(1):9-12 CASE HISTORY Figure 2: Dorsal view of both forearms Mr A is an 80 year old man who presents with several warty skin lesions on his forearms for past 6 months. There was no complaint of pain or itch except occasional irritation when he accidentally rubbed against them. He noticed that these skin lesions had gradually increased in size and number. Mr A is generally well and healthy with a functional age of 65 years. He does not have any medical problem except for mild hypertension controlled well with atenolol 100mg daily. He used to work as a Chinese opera singer in his younger days and is now retired. Currently he spends his time providing service in church and help to make handicrafts to raise funds for the church and charitable old folk’s homes. Figure 3: Closer dorsal view of right forearm Physical examination (Figures 1-3) reveals extensive solar damaged skin on sun exposed areas of both forearms. There are scattered areas of hyperpigmentation (solar lentigo), isolated patches of hypopigmentation (solar hypomelanosis), skin atrophy, presence of wrinkles, telangiectasia and superficial areas of ecchymosis.
    [Show full text]