1Department of Medicine & Rheumatology, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, India; 2Department of Internal Medicine, Government Medical College, Kozhikode, India *Corresponding Author’s e-mail: raveendranav@yahoo.co.in بنت مراهقة مصابة بتضخم مرتق يف األصابع تقرير حالة ومعايري تشخيصية مقرتحة لفرط النمو الالمتناسب الورمي الشحمي بينوي بول و رافني دران abstract: Macrodystrophia lipomatosa (ML) is a rare congenital non-hereditary condition caused by an increase in all mesenchymal elements. We report a 14-year-old girl who presented to the Medical Outpatient Department, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, India, in 2017 with progressive enlargement of digits. An X-ray and T1-weighted magnetic resonance imaging scan showed enlargement of the phalanges of the middle and index finger of the left hand with an overgrowth of soft tissues. The patient was subsequently diagnosed with ML. As the condition is benign and usually asymptomatic, no medical treatment was deemed necessary. This report describes a case of ML and proposes a set of diagnostic criteria to aid clinicians in the differential diagnosis of the condition. Keywords: Congenital Disorders; Gigantism; Macrodactyly of the Hand; Differential Diagnosis; Case Report; India. كل يف لزيادة نتيجة املر�س النادرة. الوراثية غري اخللقية الأمرا�س من واحداً ال�شحمي الورمي الالمتنا�شب النمو فرط يعد امللخ�ص: الوقفي كونهتهاريوفاي مل�شت�شفى اخلارجي الطب لق�شم ح�رصت عاما �شنها فتاة بحالة تقريرا هنا ونقدم املتو�شطة. اللحمة عنا�رص اخلريي لكلية الطب التذكارية يف كوزيكود بالهند يف عام 2017م، وهي م�شابة بت�شخم متطور يف الأ�شابع. واأظهرت نتيجة فح�س الأ�شعة ال�شينية و�شورة الرنني املغنطي�شي )T1-weighted( ت�شخما يف �شالميات الأ�شبع الأو�شط وال�شبابة، مع منو مفرط يف الأن�شجة الرخوة. م�شحوبة وغري حميدة احلالة اأن ومبا . ْحِميُّ ال�شَّ الَوَرِميُّ ُمَتَنا�شُب الالَّ النُُّموِّ َفْرُط اأنها على الفتاة تلك حالة ت�شخي�س مت ذلك على وبناء ْحِميُّ و ونقرتح ُمَتَنا�شُب الَوَرِميُّ ال�شَّ باأعرا�س، راأينا اأنه لي�س هنالك داع لأي عالج طبي للحالة. نقدم يف هذا التقرير حالة لَفْرُط النُُّموِّ الالَّ اأي�شا عددا من املعايري الت�شخي�شية مل�شاعدة الأطباء ال�رصيريني يف الت�شخي�س التفريقي لها. الكلمات املفتاحية: الأمرا�س اخللقية؛ عملقة؛ �شخامة الأ�شابع/اليد؛ الت�شخي�س التفريقي؛ تقرير حالة؛ الهند. An Adolescent with Progressive Enlargement of Digits Case report and proposed diagnostic criteria for macrodystrophia lipomatosa Binoy J. Paul1 and *Raveendran A. V.2 case report Sultan Qaboos University Med J, November 2018, Vol. 18, Iss. 4, pp. e553–556, Epub. 28 Mar 19 Submitted 10 Jun 18 Revision Req. 8 Jul 18; Revision Recd. 17 Jul 18 Accepted 2 Aug 18 doi: 10.18295/squmj.2018.18.04.023 First described in 1926, macrodystrophia lipomatosa (ML) is a rare congenital non-hered- itary condition characterised by the progressive enlargement of one or more digits of the extremities, resulting in unilateral localised gigantism.1,2 The condition is usually present at birth and stops at puberty.3–5 A variety of terms are often used to describe ML cases, such as macromelia, digital or limited gigantism, megalo- or macro- dactyly, partial acromegaly, dactylomegaly, macroceir and club finger.3,4,6 The hallmark of ML is an increase in all mesen- chymal elements of the affected digits, particularly the fibro-fatty tissue.4 In addition to the subcutaneous tissue, this condition can also affect the nerve sheath, muscle, periosteum and bone marrow.7 Usually, ML affects the median nerve distribution area of the upper limbs and the medial plantar nerve distribution area of the lower limbs.3–5 Most commonly, it affects the middle and index fingers; in the lower limbs, it usually causes enlargement of the first-to-third toes.2–5 Like Proteus syndrome, ML is a form of true macro- dactyly where there is progressive hypertrophy of all mesenchymal elements, whereas an increase in a single mesenchymal element results in pseudo-macro- dactyly, such as in neurofibromatosis type 1, fibrolipo- matous hamartoma (FLH) of the median or ulnar nerves and certain vascular malformations and acquired cond- itions (i.e. chronic hyperaemia).3–5 Although the exact pathogenesis of ML is unknown, proposed mechanisms include lipomatous degeneration, disturbed fetal circul- ation, an imbalance in growth-inhibiting factors, the trophic influence of a tumefied nerve and errors in segment- ation.6,8,9 This report describes a case of ML and pro- poses a set of diagnostic criteria to aid clinicians in the differential diagnosis of this condition. Case Report A 14-year-old girl presented to the Medical Outpatient Department, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, India, in 2017 with progr- essive enlargement of her left middle and index fingers over the previous three years [Figure 1]. No systemic symptoms were reported. At birth, her parents had An Adolescent with Progressive Enlargement of Digits Case report and proposed diagnostic criteria for macrodystrophia lipomatosa e554 | SQU Medical Journal, November 2018, Volume 18, Issue 4 no evidence of any tenderness or cutaneous changes. The rest of the systemic examination was normal and the results of routine blood examinations were within normal limits. An X-ray of the left hand showed enlargement of the phalanges of the middle and index fingers with overgrowth of soft tissues [Figure 2]. A T1-weighted magnetic resonance imaging (MRI) scan showed enlarged phalanges with increased thickness of the subcutaneous fat planes [Figure 3]. Sagittal short-tau inversion recovery images confirmed the increased subcutaneous fat by signal suppression. These findings were consistent with a diagnosis of ML. The benign nature of the condition was explained to the patient and her parents. No cosmetic treatment was requested. Discussion The differential diagnosis of ML includes FLH, neurofibr- omatosis (e.g. plexiform neurofibroma), haemangioma- tosis, lymphangiomatosis, Ollier disease and Proteus, Beckwith-Wiedemann, Maffucci and Klippel-Trénaunay- Weber syndromes.4,5 Overall, FLH can be differentiated from ML as the former usually produces isolated nerve lesions associated with intramuscular fat deposition, whereas fat deposition in the latter occurs in the nerve sheath as well as the subcutaneous and muscle comp- artments.4,5 In ML, there is also periosteal involvement resulting in bony changes like hypertrophy, exostosis and ankylosis in the interphalangeal joint and fatty invasion of the medullary cavity.4,5 In contrast, macro- dactyly secondary to hyperaemia due to haemangio- matous or lymphangiomatous overgrowth produces only soft tissue hypertrophy. In addition, the absence of cutaneous and vascular abnormalities help to eliminate the possibility of Klippel-Trénaunay-Weber syndrome, while the absence of enchondromas precludes Ollier disease.4,5 In plexiform neurofibromatosis, overgrowth is often bilateral and either continues after puberty or stops prior to this stage due to the premature fusion of the growth plate as a result of haemangiomatous elements; in comp- arison, ML cases are rarely bilateral and growth ceases at puberty.4 Moreover, ML predominantly affects the distal phalanges. In neurofibromatosis, the enlarged osseous structures have a wavy cortex and an elongated sinuous appearance contrasting with that of ML cases; additionally, soft-tissue lucencies due to the neuro- cutaneous manifestations of neurofibromatosis are absent in ML.10 The authors propose a set of diagnostic criteria to help clinicians in the differential diagnosis of ML cases [Table 1]. The presence of essential clinical criteria along noticed a slight enlargement of her left middle finger. However, there was no family history of similar conditions or a personal history of any significant illnesses. An examination of her left hand showed diffuse overgrowth of the middle and index fingers. The affected fingers had the same consistency as her other fingers, with Figure 1: Photograph of the hands of a 14-year-old girl showing enlargement of the left middle and index fingers. Figure 3: T1-weighted magnetic resonance imaging scan of the left hand of a 14-year-old girl showing enlarge- ment of the phalanges of the middle and index fingers, with excess fibro-fatty tissue around the affected digits. Figure 2: X-ray of the left hand of a 14-year-old girl showing enlargement of the phalanges of the middle and index fingers, with bony and soft tissue overgrowth. Binoy J. Paul and Raveendran A. V. Case Report | e555 appearance of fat within a nerve sheath excludes the possibility of neurofibromatosis.5 In addition, neurofibr- omas demonstrate marked hyperintensity close to the nerves in T2-weighted images; in FLH, MRI scans show enlargement of the fusiform nerve due to thickened nerve fibre embedded in fatty tissue.15 Patients with ML are usually asymptomatic, although some can develop mechanical problems resulting from secondary degenerative changes in the joint and the compression of the neurovascular structure (i.e. carpel or tarsal tunnel syndromes).4 Patients may also have functional issues, such as difficulty in grasping objects or, rarely, abnormal gait due to overgrowth of the affected region.4,6,16 Other problems seen in ML cases include lipomatous growths in the intestines as well as other tissues, naevus pigmentation, calvarial abnormalities, pulmonary cysts, syndactyly, polydactyly, clinodactyly, brachydactyly and symphalangism.4 As ML is usually benign, medical attention is gener- ally only necessary for cosmetic or aesthetic reasons.4 For those requiring surgical treatment, multiple debulking procedures, epiphysiodesis and osteotomies can be performed; however, such procedures can be challenging as there is a 33–60% risk of recurrence and a 30–50% risk of nerve injury due to overzealous debulking.2,17 For patients with severe ML-related functional and aesthetic concerns, amputation is an option.2 In children, the rate of growth of the affected digit can be slowed by destroying, stapling or wiring the epiphyseal plate.18 with either histopathological or radiological criteria is required for the diagnosis of ML. The histopathological analysis of ML cases generally reveals an increase in adipose tissue scattered in fine mesh-like fibrous tissue.4,11 Plain X-rays show an overgrowth of soft tissue and bony elements, along with radiolucent areas due to the presence of adipose tissue. Soft tissue overgrowth is usually seen more in the volar aspect, resulting in dorsal deviation, while bony overgrowth increases the width and length of the affected phalanges with distal splaying, resulting in a mushroom-like appearance.7 Secondary osteoarthritis changes—like joint space narrowing, sub- chondral cysts and osteophytes—may also be seen in adult patients.12 Ultrasonography typically shows diffuse echogenicity consistent with increased fat accumulation in the subcutaneous and muscle tissues; this results in a loss of soft tissue detail and a decrease in grayscale reflectivity between soft tissue structures.13 Computed tomography reveals bony overgrowth, excessive fat proliferation and, with muscle involvement, separation of the muscle fibres due to fatty infiltration.14 Typically, MRI scans show fatty infiltration of the muscles, cortical thickening and bony overgrowth.14 They may also show abundant fat tissue in the affected area, with the same low signal intensity as that of normal sub- cutaneous fat on T1- and T2-weighted MRI sequences. Linear hypointense bands in redundant adipose tissue represent fibrous strands.5 The absence of encapsulation helps to differentiate ML from a lipoma, while the Table 1: Proposed diagnostic criteria for cases of macrodystrophia lipomatosa Type of criteria Diagnostic necessity/certainty Description Clinical Essential • Unilateral localised gigantism, most commonly involving the median nerve area (first three fingers) in the upper limbs or the medial planter nerve area (first three toes) in the lower limbs • Lack of family history of similar conditions • No cutaneous changes • No systemic symptoms • Cessation of digit enlargement at puberty Optional • Presence of digit enlargement at birth • Presence of related issues (i.e. syndactyly, polydactyly, clinodactyly, brachydactyly, etc.) Histopathological Confirmatory • Evidence of an increase in all mesenchymal elements • Evidence of increased adipose tissue scattered in a fine mesh-like fibrous tissue • Evidence of both soft tissue and bony elements, with predominant fibro-fatty tissue hypertrophy Radiological Possible • X-ray evidence of overgrowth of both soft tissue and bony elements Probable • CT evidence of bony overgrowth, excessive fatty proliferation and separation of the muscle fibres Confirmatory • MRI evidence of fatty infiltration of the muscles, cortical thickening and bony overgrowth of the affected area • MRI evidence of increased thickness of the subcutaneous fat planes with linear hypointense fibrous bands in the adipose tissue without encapsulation • MRI evidence of fat within the nerve sheath CT = computed tomography; MRI = magnetic resonance imaging. An Adolescent with Progressive Enlargement of Digits Case report and proposed diagnostic criteria for macrodystrophia lipomatosa e556 | SQU Medical Journal, November 2018, Volume 18, Issue 4 7. Gupta SK, Sharma OP, Sharma SV, Sood B, Gupta S. Macro- dystrophia lipomatosa: Radiographic observations. Br J Radiol 1992; 65:769–73. https://doi.org/10.1259/0007-1285-65-777-769. 8. Kelikan H. Congenital Deformities of the Hand and Forearm. Philadelphia, Pennsylvania, USA: Saunders, 1974. Pp. 610–60. 9. Barsky AJ. Macrodactyly. J Bone Joint Surg Am 1967; 49:1255–66. https://doi.org/10.2106/00004623-196749070-00001. 10. Pitt MJ, Mosher JF, Edeiken J. Abnormal periosteum and bone in neurofibromatosis. Radiology 1972; 103:143–6. https://doi. org/10.1148/103.1.143. 11. Rohilla S, Jain N, Sharma R, Dhaulakhandi DB. Macrodystro- phia lipomatosa involving multiple nerves. J Orthop Traumatol 2012; 13:41–5. https://doi.org/10.1007/s10195-011-0159-6. 12. van den Heever AJ. Macrodystrophia lipomatosa. S Afr J Radiol 2014; 18:a667. https://doi.org/10.4102/sajr.v18i2.667. 13. Sone M, Ehara S, Tamakawa Y, Nishida J, Honjoh S. Macro- dystrophia lipomatosa: CT and MR findings. Radiat Med 2000; 18:129–32. 14. Cerofolini E, Landi A, DeSantis G, Maiorana A, Canossi G, Romagnoli R. MR of benign peripheral nerve sheath tumors. J Comput Assist Tomogr 1991; 15:593–7. https://doi.org/10.1097 /00004728-199107000-00013. 15. Soler R, Rodríguez E, Bargiela A, Martĩnez C. MR findings of macrodystrophia lipomatosa. Clin Imaging 1997; 21:135–7. https://doi.org/10.1016/0899-7071(95)00095-X. 16. Wu KK. Macrodactylia fibrolipomatosis of the foot. J Foot Surg 1991; 30:402–5. 17. Brodwater BK, Major NM, Goldner RD, Layfield LJ. Macro- dystrophia lipomatosa with associated fibrolipomatous hamar- toma of the median nerve. Pediatr Surg Int 2000; 16:216–18. https://doi.org/10.1007/s003830050728. 18. Tsuge K. Treatment of macrodactyly. Plast Reconstr Surg 1967; 39:590–9. https://doi.org/10.1097/00006534-196706000- 00008. Conclusion In summary, ML is a rare congenital non-hereditary condition resulting in localised gigantism. The condition is usually asymptomatic and treatment is for cosmetic reasons. This report describes a case of ML and proposes a set of diagnostic criteria to aid clinicians in accurately differentiating ML from other conditions with similar presentations. References 1. Feriz H. [Progressive macrodystrophia lipomatosa]. Virchows Arch Pathol Anat Physiol Klin Med 1926; 260:308–68. https://doi.org/10.1007/BF01888444. 2. Prasetyono TO, Hanafi E, Astriana W. A review of macrodys- trophia lipomatosa: Revisitation. Arch Plast Surg 2015; 42:391–406. https://doi.org/10.5999/aps.2015.42.4.391. 3. Tuzuner T, Parlak AH, Kavak A, Alper M. A neglected case of macrodystrophia lipomatosa of the foot in an elderly man. J Am Podiatr Med Assoc 2005, 95:486–90. https://doi.org/10.75 47/0950486. 4. Khan RA, Wahab S, Ahmad I, Chana RS. Macrodystrophia lipomatosa: Four case reports. Ital J Pediatr 2010; 36:69. https://doi.org/10.1186/1824-7288-36-69. 5. Boren WL, Henry RE Jr, Wintch K. MR diagnosis of fibro- lipomatous hamartoma of nerve: Association with nerve territory-oriented macrodactyly (macrodystrophia lipomatosa). Skeletal Radiol 1995; 24:296–7. https://doi.org/10.1007/BF001 98419. 6. Littler WJ, Cramer LM, Smith JW, Eds. Symposium on Recons- tructive Hand Surgery: Proceedings of the Symposium of the Educational Foundation of the American Society of Plastic and Reconstructive Surgeons. St Louis, Missouri, USA: Mosby, 1974. Pp. 218–20.