An Adolescent with Progressive Enlargement of Digits Case report and proposed diagnostic criteria for macrodystrophia lipomatosa

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.


F
irst described in 1926, macrodystrophia lipomatosa (ML) is a rare congenital non-hereditary condition characterised by the progressive enlargement of one or more digits of the extremities, resulting in unilateral localised gigantism. 1,24][5] A variety of terms are often used to describe ML cases, such as macromelia, digital or limited gigantism, megalo-or macrodactyly, partial acromegaly, dactylomegaly, macroceir and club finger. 3,4,6he hallmark of ML is an increase in all mesenchymal elements of the affected digits, particularly the fibro-fatty tissue. 4In addition to the subcutaneous tissue, this condition can also affect the nerve sheath, muscle, periosteum and bone marrow. 7][4][5] Like Proteus syndrome, ML is a form of true macrodactyly where there is progressive hypertrophy of all mesenchymal elements, whereas an increase in a single mesenchymal element results in pseudo-macrodactyly, such as in neurofibromatosis type 1, fibrolipomatous hamartoma (FLH) of the median or ulnar nerves and certain vascular malformations and acquired conditions (i.e.4][5] Although the exact pathogenesis of ML is unknown, proposed mechanisms include lipomatous degeneration, disturbed fetal circulation, an imbalance in growth-inhibiting factors, the trophic influence of a tumefied nerve and errors in segmentation. 6,8,9This report describes a case of ML and proposes a set of diagnostic criteria to aid clinicians in the differential diagnosis of this condition.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.

Case Report
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, neurofibromatosis (e.g.plexiform neurofibroma), haemangiomatosis, lymphangiomatosis, Ollier disease and Proteus, Beckwith-Wiedemann, Maffucci and Klippel-Trénaunay-Weber syndromes. 4,5Overall, 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 compartments. 4,5In 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. 4,5In contrast, macrodactyly secondary to hyperaemia due to haemangiomatous 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 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 comparison, 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 neurocutaneous 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   appearance of fat within a nerve sheath excludes the possibility of neurofibromatosis. 5In addition, neurofibromas 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. 15atients 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). 4Patients may also have functional issues, such as difficulty in grasping objects or, rarely, abnormal gait due to overgrowth of the affected region. 4,6,16Other 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. 4s ML is usually benign, medical attention is generally only necessary for cosmetic or aesthetic reasons. 4For 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. 2,17or 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. 18th 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. 4,11lain 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. 7Secondary osteoarthritis changes-like joint space narrowing, subchondral cysts and osteophytes-may also be seen in adult patients. 12Ultrasonography 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. 13Computed tomography reveals bony overgrowth, excessive fat proliferation and, with muscle involvement, separation of the muscle fibres due to fatty infiltration. 14ypically, MRI scans show fatty infiltration of the muscles, cortical thickening and bony overgrowth. 14They may also show abundant fat tissue in the affected area, with the same low signal intensity as that of normal subcutaneous fat on T1-and T2-weighted MRI sequences.Linear hypointense bands in redundant adipose tissue represent fibrous strands. 5The absence of encapsulation helps to differentiate ML from a lipoma, while the

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.

A 14 -
year-old girl presented to the Medical Outpatient Department, Kunhitharuvai Memorial Charitable Trust Medical College, Kozhikode, India, in 2017 with progressive 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 e554 | SQU Medical Journal, November 2018, Volume 18, Issue 4

Figure 1 :
Figure 1: Photograph of the hands of a 14-year-old girl showing enlargement of the left middle and index fingers.

Figure 3 :
Figure 3: T1-weighted magnetic resonance imaging scan of the left hand of a 14-year-old girl showing enlargement of the phalanges of the middle and index fingers, with excess fibro-fatty tissue around the affected digits.

Figure 2 :
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.

Table 1 :
Proposed diagnostic criteria for cases of macrodystrophia lipomatosa 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.