MINISTER OF TRAINING AND EDUCATION MINISTER OF HEALTH HANOI MEDICAL UNIVERSITY ======= NGUYEN HONG SON TREATMENT OF GIANT CONGENITAL MELANOCYTIC NEVUS BY SERIAL EXCISIONS AND TISSUE EXPANSION Major Re[.]
MINISTER OF TRAINING AND EDUCATION MINISTER OF HEALTH HANOI MEDICAL UNIVERSITY ======= NGUYEN HONG SON TREATMENT OF GIANT CONGENITAL MELANOCYTIC NEVUS BY SERIAL EXCISIONS AND TISSUE EXPANSION Major: Reconstructive orthopedic and plastic surgery Code: 9720104 ABSTRACT OF MEDICAL DOCTORAL THESIS HA NOI – 2023 The thesis has been completed at HANOI MEDICAL UNIVERSITY Supervisor: Supervisor 1: Assoc Prof Nguyen Bac Hung, MD, PhD Reviewer 1: Assoc Prof Nguyen Hong Ha Reviewer 2: Assoc Prof Dang Van Em Reviewer 3: Assoc Prof Tran Van Anh The thesis will be present in front of board of university examiner and reviewer lever at on 2023 This thesis can be found at: National Library Hanoi Medical University Library THE LIST OF WORKS HAS PUBLISHED AND RELATED TO THE THESIS Son N.H., Hung N.B., Son T.T (2020) “Initial results of serial excisions for giant congenital melanocytic nevus treatment” Journal of Medical Research, Issue 132, volume 8, november 2020, p 112 - 119 Son N.H., Hung N.B., Son T.T (2020) “Initial results of tissue expanded flap for giant congenital melanocytic nevus treatment” Journal of Medical Research, Issue 132, volume 8, november 2020, p 103 - 111 Son N.H., Hung N.B., Son T.T., Dung P.T.V (2022) “Treatment of giant congenital melanocytic nevus by serial excisions and tissue expansion” Vietnam Medical Journal, september Issue - Thematic Issue, 2022, volume 518, p 524 - 530 INTRODUCTION Giant congenital melanocytic nevus (GCMN) is a limited dysplasia of embryonic origin, with the presence of centrally concentrated melanocytes clusters or bands, in the dermis and skin appendages Immunohistochemistry with antibodies to S100 and HMB-45 helps to confirm the origin of the nevus cells Giant congenital melanocytic nevus has clinical features that look like patches of skin, black or brown, clearly, or indistinctly demarcated, rough, or smooth surface, with many hard black or soft brown hairs on the surface They often appear immediately after birth with a large size and area, occupying one or more anatomical skin units Surgical treatment of GCMN includes two main things: Excision and reconstruction of the skin defect Direct suture removal, local flaps, adjacent flaps with seamless pedicles, and microsurgical flaps are difficult to solve independently, but they are complementary to other surgeries Free skin grafts can cover defects after the removal of lesions, but skin grafts are often dark and unsightly Skin expansion surgery including natural skin expansion (serial resection) and skin expansion by tissue expanders are the two main surgical methods used to treat GCMN The method of skin expansion can solve both major problems in GCMN surgery, which are cancer prevention and the best cosmetic improvement for the patient In the world, GCMN has been studied very early with a series of research by authors such as Domokos, Arneja, Fitzpatrick on clinical, histopathological, and treatment methods In Vietnam, Vu The Duyen and Do Dinh Thuan also researched and reported on benign melanoma cells in the maxillofacial region However, we have not seen any research on GCMN We conduct the research: "Treatment of giant congenital melanocytic nevus by skin expansion techniques" with the two main objectives as follows: To describe the clinical and subclinical features of giant congenital melanocytic nevus To evaluate results and propose indications for surgery of giant congenital melanocytic nevus by skin expansion techniques New contributions of the thesis This is the first research in Vietnam that mentions the clinical and subclinical features of giant congenital melanocytic nevus and the results of giant congenital melanocytic nevus surgery by skin expansion techniques This is a systematic and full research with a reliable number of subjects Describe quite systematically and fully the clinical features including identification, size, and location of the fibrillation; Risk features for malignancy and subclinical features including histopathology and immunohistochemistry Evaluating the results of skin expansion surgery and proposing indications for natural skin expansion surgery, skin expansion by tissue expanders to treat GCMN These are new scientific and practical contributions to Plastic Surgery The layout of the thesis The thesis has 121 pages including: Introduction (02 pages), overview (30 pages), materials and methods (18 pages), results (25 pages), discussion (44 pages), conclusion, recommendation (02 pages) The thesis has 26 tables, charts, 54 figures, and 137 references in Vietnamese and English OVERVIEW 1.1 Skin anatomical and physiological features 1.1.1 Skin anatomical features Human skin is composed of layers: epidermis, dermis, and hypodermis The blood supply system for the skin includes a direct artery system or an indirect artery for branches to form vascular networks There are 40 skin areas with a clear limit of the blood acute of the skin artery called the anatomical area of the skin artery This limit is broken when the main source is lost There are many ways to calculate skin area: by age, weight, height Costello or Mosteller's specific method of calculating skin area is based on the patient's height and weight The skin is divided into three distinct anatomical regions: head and neck, trunk, and extremities Each region consists of many different anatomical units and subunits The head and neck region include the head (top, occipital, temples, and forehead), face (eyes, nose, mouth, chin, cheeks, ears), and neck The body area includes the chest, abdomen, back, and waist The limb area includes the hands (armpits, arms, elbows, forearms, hands) and legs (buttocks; thighs, hamstrings; legs, feet) 1.1.2 Skin physiological features The origin of melanocytes is the neural crest Melanoblasts are embryonic cells capable of producing melanocytes Melanocytes are cells that produce and contain melanin Melanocytes are interspersed with basal cells at a ratio of 1/36 to 1/50 Hematoxylin – Eosin dyed; they are bright The stem is in contact with the basement membrane but is not connected, with many cytoplasmic branches, a large kernel, dark color, and alkaline cytoplasm Biomechanics is one of the biological properties of the skin before a force act on the skin for a certain time, affecting the results of shaping techniques, especially skin expansion methods There are basic properties: Stretch, elastic, consistency, mush, and expansion In whic h the property of expansion is the principle of the skin stretching technique if maintaining traction for several days Macroscopically, it is difficult to distinguish between normal and dilated skin, but when examined under optical and electron microscop y, skin structures change over time immediately after the insertion of the expansion system Changes include the epidermis, dermis, and hypodermis Skin changes will recover in to years 1.2 Clinical and subclinical features 1.2.1 Clinical features GCMN has four main identifying features: color, surface, border, and hair on the nevus The majority of GCMN clinically present as a patchlike patch of skin that appears immediately after birth, growing over 20 cm The common form is black, clearly borderline, rough surface, and many hard black hairs The singular form has opposite features, brown lesions, unknown boundaries, flat surface, and soft brown hairs Nevus melanocytes are prone to malignant degradation, so GCMN is at high risk of malignancy The risk of malignancy ranges from 5% to 15%, depending on many factors such as abnormal progression, patient age, number of satellites, and 'malignant' location When GCMN becomes cancerous, they often have warning signs and all share the same word 'change' including changes in color, surface, and boundaries GCMN in the majority of cases appears immediately after birth and tends to be stable The incidence of giant congenital melanocytes between men and women is not different GCMN may be accompanied by other birth defects such as liposarcoma, and neurofibromatosis Cutaneous neurotrophic melanoma syndrome is rare and very severe, children often die prematurely 1.2.2 Subclinical features Histopathology with HE stains helped confirm the diagnosis of melanocytic nevus Based on the cell morphology and tissue structure, the melanocytic nevus is divided into three histopathological types: junctional, compound, or intradermal In the compound form, the nevus melanocytes have features of both junctional and intradermal Histopathology is also valuable for the early diagnosis of cancer Immunohistochemistry is a combination of immunological responses to dyes that reveal antigens in cells Each cell type has different specific antigens Detection of specific antigens will confirm cell origin The S100 antibody will help localize the cells of histiocytic or neural origin, while the HMB-45 antibody will confirm the cells are of nevus melanocyte origin The ultrastructural features of nevus melanocytes on electron microscopy are similar to those of melanocytes The difference is that they lack dendrites; instead of having microvilli Melanocytes contain more organelles cytoplasm, with larger cytoplasm and nucleus, with indentations Melanosomes in the cytoplasm produce melanin 1.3 Diagnosis The definitive diagnosis of GCMN is based on clinical features such as the primary, time of occurrence, size, area, or anatomical unit of the neuron Histopathology and immunohistochemistry confirmed the diagnosis The largest diameter of the nevus is the most common diagnostic criterion In addition, the area and anatomical unit are of definite diagnostic factors A nevus is called a giant when it satisfies one of the following criteria: - The nevus has the size of the largest diameter of 20 cm or more in adults; reaches 20 cm when adults in and young children; Or from cm or more at the head, and cm in the physical limb with the infant - The nevus has an area of 120 cm or more, or 2% or more of the body area when the nevus is in any position, or 1% or more of the area when the nevus is at the head and neck, hand, or foot - The nevus is located in an anatomical unit For young children, it is possible to apply the estimation formula of Ana Carolina Leite Viana (2012) This chart applies to both male and female children at the head and neck, trunk, or extremities 1.4 TREATMENT 1.4.1 The procedure for giant congenital melanocytic nevi Although procedures such as tangential excision, curretage, dermabrasion, chemical peel, cryotherapy, ablation, radiotherapy, and laser therapy… are not able to completely remove all nevus cells, they may remove some parts of the superficial nevi which can decrease the risk of cancer Additionally, it also brings a better appearance to the patient Lesions become lighter in color and more aesthetic 1.4.2 Surgery therapy for giant congenital melanocytic nevi Reasons of removing GCMN Surgery therapy shows the ability to completely remove all nevus cells within the excised lesion, therefore, the risk of cancer can be prevented Mahajan suggested five reasons associating with the risk of malignancy and aesthetics: signs of malignancy, abnormal progression, “malignant” location, the feeling of worry about the risk of cancer, anxiety of aesthetic issue Time to remove GCMN Choosing the right time of surgery is considered as a big issue, including many problems such as eliminating the risk of malignancy, the aesthetical issue and the problems of anesthesia and surgery as well To prevent the risk of malignancy, Fitzpatrick recommends that surgery should be operated when the child is over months Regarding to aesthetics, Andrew recommends completing surgery under the age of Regarding to anesthesia: children over years with the weight more than 10kg Surgery therapy for GCMN removal The lesion was completely resected, 1-3 mm from the border of lesion with the depth equally to subcutaneous layer, and superficial fascia or partial removal The resection is often related to aesthetics and exposure areas The lesion will be excised completely in one surgery or serial excisions The method of covering for each excision can be like or different from the technique of natural skin expansion Reconstructive surgery after removal of GCMN Using natural skin expansion or an expander depends on the location the size of nevi and the age of patient These are two main techniques that have been used to cover skin defect after GCMN removal Skin grafting is a technique applied widely to cover large skin defects in general and GCMN Local flaps and distant flaps are complementary therapies for skin expansion techique 1.5 GCMN TREATMENT 1.5.1 GCMN treatment with the skin expansion technique 1.5.1.1 Natural skin expansion M Marquet is the one who reinvents the concept of natural skin expansion after excision which uses skin tension after surgery as the driving force to stretch the skin The principle of this technique is that the response of skin under tension undergoes three stages: stretching, relaxation, and proliferation Natural skin expansion is indicated for completely benign GCMN that cannot be completely removed in one surgery and includes all these bellowing features: no malignant transformation, large and elastic surrounding skin with mobility of covering the defect Natural skin expansion is suitable for young children, the area of neck, face, torso, buttocks, thighs, and arms Less than surgeries needed to completely remove the lesion; the mobilized healthy skin has a suitable structure and can be mobilized from many directions 1.5.1.2 Skin expansion by tissue expanders Tissue expanders were developed in 1956 when Charles Neumann published the first case of skin expansion with latex expander to reconstruct the ear Next, Radovan designed a skin expansion system consisting of a silicone bag, a closed expansion system, and a serum dilation pump Natural skin expansion is indicated for completely benign GCMN, without malignant transformation Skin flap from expansion can be used as local flaps, distant flaps or as materials for skin grafting Natural expansion is suitable for older children with enough commitment; suitable for the position of the scalp, face, and extremities, especially forearms and legs; require more than episodes of excision to completely remove the lesion; The surrounding healthy skin is not enough or cannot be mobilized 1.5.1.3 Complementary surgery, combined treatment of GCMN Free skin grafting T T H Thuy reported a case of free skin grafting for facial GCMN in a 31-month-old female patient The nevi occupied nearly the entire left half of the face, measuring x cm The outcome after 28 months, the skin graft on the forehead did not change color, did not grow hair, the scar line was soft, and no stretching Facial skin grafts are usually associated with hyperpigmentation and darker color The scars are highly aesthetic Skin flaps Local flaps for GCMN treatment T T Son used pocket expander to treat a GCMN that occupied the entire circumference of the right arm and elbow The maximum length of the tumor is up to 26cm, the widest place equivalent to the arm circumference is 17cm Thus, with the flap created from a meticulous tissue expander, it was possible to cover the defect of almost the entire arm and elbow However, skin flap surgery is still needed to complete the surgery Distant flap for GCMN treatment T T Son announced the use of a pedicled distant flap to successfully treat a 45-year-old male patient with GCMN occupying nearly the entire arm Combined surgery In fact, many GCMN patients are very large in size and area It is very difficult to cover the skin defect after excision of the entire lesion Although natural skin expansion or tissue expanders may create a large size of skin, equivalent to cover skin defects after removal of the lesion, but with too large lesions, in difficult size, the combination of techniques of skin expansion or combined with free skin grafting is remained a suitable solution The phase of creating a skin flap also encounters many difficulties, especially the lack of flap area to cover skin defect After resection of the lesion, the incision edges tend to be wider Skin flaps after shaping tend to shrink causing coverage to sometimes be lacking The calculation of the skin flap's rotation angle, the flap's extension is sometimes not really accurate Free skin grafts to compensate for these deficiencies are needed 1.5.2 GCMN treatment with skin expansion technique in Vietnam and worldwide 1.5.2.1 Natural skin expansion for GCMN treatment in Vietnam Many domestic authors have published clinical cases or series of GCMN cases treated by natural skin expansion technique In the scalp, face and neck area, Dung performed natural skin expansion surgery for a 3-year-old child with GCMN in the right forehead area with the size x cm Entire GCMN was excised Scars are thin and soft, highly aesthetic, not deform the hairline of the forehead and eyebrows In the trunk area, Son performed natural skin expansion surgery for a 6-year-old female patient with GCMN in the back, the left posterior wall of the abdominal thoracic wall The outcome after surgeries, the entire nevi was removed, T-shaped scars across the waist and along the spine, physiological scar direction, slightly stretched scars 10 2.3.3 Study procedures 2.3.3.1 Patient sclection Examination and tests to confirm the diagnosis of GCMN Consent to treatment, research Treatment: identification of lesions and surrounding healthy skin, selection of patients, selection of surgical methods 2.3.3.2 Surgery procedures Natural skin expansion surgery Treatment planning: assessment of lesions, characteristics of the site of skin dilatation, time of surgery, how to remove the lesion, expected scar line First natural skin expansion surgery: Design two equal skin incisions above the lesion, which are parallel to the skin Langer’s lines Put patient under nesthesia or anesthesia Excise the lesion from the center or the periphery Do not peel off the edge Suture with tension Serial natural skin expansion surgeries afterwards: The interval between surgeries is 3-6 months The procedure is like the first surgery If the number of surgeries needed exceeds 5, consider pocket tissue expander Last natural skin expansion surgery: The last surgery is like the previous ones It should be noted: the skin incision is always on the normal skin to avoid trauma to the skin edge Peel off the edge incision edge to reduce tension, close the incision in layers without tension Post-operative care: Monitor, change dressings daily, drain drainage after 24 hours, remove sutures after 7-14 days, complete medical records Surgery with pocket tissue expander Treatment planning: Lesion assessment, location of dilation system, choice of dilatation system, skin incision, expected flap Surgery to place expander pocket: Put patient under anesthesia or anesthesia Skin incision Install the expansion system, check, and make sure the system is not punctured Close the incision in layers Inject saline 10% into pocket Wound dressing Expansion pump: According to the schedule: pump 1-2 times a week, each time up to - 14% of the bag volume Continuous expansion by electric pump helps to shorten the time Flap reconstructive surgery: Patient preparation Pump an additional amount of - 10% of bag volume Remove the expansion system Flap creation: flap design (in situ or remote flap or free skin graft) Place the flap over the lesion Cut off the lesion Suture Post-operative care: change dressings daily, drain drainage after 24 hours, remove sutures after 7-14 days, complete medical records Combined and Complementary Surgery Combination of natural skin extension and tissue expander Free skin grafting, local flap, remote flap 11 2.3.3.3 Assessment of surgery results Evaluate results immediately after each surgery Time of assessment: day 1, suture removed Evaluation criteria: criteria and levels: good, average, poor - Skin flap vitality: good flap, malnourished flap, poor: necrotic flap - The first stage of scar healing: good scar healing, slow healing, no healing - Complications: uncomplicated, mild complications, severe complications - Area of resection: good: remove the entire lesion in surgery, remove as planned, remove less than planned - Additional surgery: no need, flap deficiency less than 10% of the area, flap deficiency over 10% of the area Evaluation of results after completing surgery Evaluation time: after 3, and 12 months Evaluation criteria: criteria and levels - Scar condition: assess thinness, flatness, density, skin color, stretch achieving - criteria, - criteria, 0-1 criteria - Condition of flap: assess density, color, thickness, surface, hair achieving - criteria, - criteria, 0-1 criteria Traction condition: no traction, mild traction, significant traction - Recurrence status: no recurrence, recurrent but benign, malignant - Resection ability: can remove the entire lesion, over 75% of the area can be removed, less than 75% of the area can be removed Evaluate the results according to a few related factors By age, location, resectability, number of lesions resection 2.3.4 Indicators, variables in the study Clinical, laboratory: identification, risk of malignancy, histology Results: Subject, immediately after surgery, completed surgery 2.3.5 Techniques used in the study Resection: whole, part; from the center, from the periphery Coverage: Natural expansion, tissue expander, additional surgery 2.3.6 How to evaluate the results of surgery Scoring: good: points, average: 1, poor: Calculate total score Very good: 9-10, good: 7-8, average: 5-6, poor: 3-4, very poor: 0-2 2.3.7 Data analysis: SPSS 16.0 software 2.4 LOCATION, TIME OF STUDY Research location: NHDV and Saint Paul Hospital Research time: From October 2014 to October 2022 2.5 RESEARCH ETHICS Ethics Council: 243/HDĐ-BVDLTW 11/28/14 12 RESULTS 3.1 CLINICAL, SUBCLINICAL CHARACTERISTICS OF GCMN Table 3.1 Clinical characteristics of GCMN (n = 49) Color Border Surface Surface Đặc điểm Well- PoorlyHard, Soft, Mammi nhận Black Brown demar demar Flat black brown -lated dạng -cated -cated hair hair n 46 45 45 44 % 93,88 6,12 91,84 8,16 91,84 8,16 89,80 10,20 Among 49 patients, the common features of GCMN include: black color (93,88%), mammilated surface (91,84%), well-demarcated border (91,84%), hard, black hair (89,80%) Table 3.2 Risk factors of malignancy (n = 49) Abnormal Number of High-risk Abnormal signs "satellite" sites progression Risk nevi factors Yes No Yes No Yes No 100