A four-year-old boy, the product of a full-term, normal, spontaneous vertex
delivery, had pain in the lower extremities with activity. The family history
was negative, and the medical history was important only for otitis media at
one year of age. The boy was seen by two local physicians, who reported that
there were no abnormalities in the lower extremities on physical examination
and specifically that no edema or soft-tissue masses were present. Radiographs
of the lower extremities were made and were later sent to us. They showed
cortical defects in the proximal aspect of the tibia bilaterally with
surrounding osseous sclerosis (Figs.
1-A and
1-B). Follow-up radiographs
made several months later showed no change in the tibial lesions, but
additional radiographs showed several radiolucent lesions in the pelvis. No
other lesions were noted in the lower extremities. The diagnosis of multiple
fibrous cortical defects was postulated at the time. No medical or surgical
interventions were recommended.
At the age of seven years, the child was referred to our facility with a
small, nontender mass in the left side of the groin. New radiographs of the
lower extremities revealed no change in the tibial or pelvic lesions, but an
additional lesion was recognized in the proximal part of the right femur.
Physical examination showed no other problems. The patient was managed with an
excisional biopsy of the mass in the left side of the groin and curettage and
allograft bone-grafting of the lesion in the proximal aspect of the right
femur. Histologic examination showed that the mass in the left side of the
groin was a cystic hygroma, and the specimen from the right femur was
consistent with the diagnosis of osseous lymphangiomatosis. Four months later,
progression of the right and left tibial lesions was noted on imaging studies
and the child was managed with curettage and allograft bone-grafting of these
sites.
Over the course of the next two years, the patient had multiple
inflammatory febrile episodes that were considered to be lymphangitis and
required multiple hospitalizations and intravenous antibiotics. When he was
eight years old, the child had a catheter placed in a cystic area within the
left calf for the dual purpose of allowing drainage of lymphatic fluid and
infusion of tetracycline. This failed to alleviate the massive swelling of the
leg and the recurrent lymphangitis (Fig.
2). He underwent a partial resection of the mass in the left lower
extremity during which 1400 g of fluid-filled tissue was removed. A subsequent
operation two months later removed an additional 850 g of lymphangiomatous
tissue. A third resection four months later resulted in the removal of
approximately the same amount of tissue. All pathology specimens were
consistent with benign neoplastic lymphatic tissue (Figs.
3-A,
3-B, and
3-C).
When the patient was nine years old, lymphangitis developed again,
requiring hospitalization and intravenous antibiotic treatment. Radiographs
revealed a lesion in the distal aspect of the right femur with impending
fracture. This was treated by curettage and allograft bone-grafting of the
lesion. The lesion healed uneventfully.
After another seven months, swelling and skin problems in the left lower
extremity required further intervention. A portacath was inserted into the
distal aspect of the left calf to drain lymphatic fluid. A mean of 1.5 L
(range, 0.5 to 2.2 L) per day was obtained from the site over the next fifteen
months. This treatment required considerable attention to diet, fluid, and
electrolyte balance and support from the patient's family. The portacath was
exchanged and repositioned after six months because of infection, and, at
fifteen months, it was removed. There was a gradual return of lymphedema and
recurrent drainage from the damaged overlying skin, despite the use of
compression garments on the lower extremities.
Approximately one year later, when he was ten years old, the patient
returned for a follow-up visit and had severe pain in the left lower
extremity. He was found to have recurrent lesions in both tibiae with a
slightly displaced fracture on the left side. Curettage and allograft
bone-grafting along with placement of an internal Kirschner wire was
performed. The Kirschner wire was chosen because it seemed to have the least
likelihood of disturbing the lymphangitic component of the medullary cavity or
increasing the possibility of cortical disruption. The patient had an
uneventful immediate postoperative course but returned within one year with a
recurrent lesion and another impending fracture. A repeat curettage and
allograft bone-grafting with Kirschner wire fixation was performed to prevent
additional fractures during the healing phase. The patient wore a long leg
cast for two weeks and subsequently wore a brace. He had a relatively
uneventful postoperative course with restoration to reasonable function by
eight weeks (Fig. 4).
When the patient was sixteen years old, in February 1998, he was started on
recombinant interferon-alpha therapy, on the basis of the successful results
described in a case report by Reinhardt et
al.17, at a dosage
of 3.5 million U/m2 alternating with 3.0 million U/m2
each day. During a period of six months, the left lower extremity
substantially decreased in size and the skin alterations covering the most
affected areas underwent a gradual, albeit incomplete, resolution. However,
the skin, especially the toes of the left foot, continued to show intermittent
breakdown (Fig. 5). After three
years, the dose of interferon was reduced to 2 million U/m2 per day
and 800 mg of celecoxib per day was added. At the latest follow-up
examination, the patient was twenty-two years old and was attending college
and leading a quite active life. He continued to have some swelling of the
soft tissues of the calf requiring supportive stockings, and he had occasional
skin breakdown around the toes. He had had no complications from the
interferon therapy other than a reduction in neutrophil count prior to
reducing the dose. The liver function studies and platelet count remained
normal. He cited fatigue and moderate intermittent myalgia as the only side
effects of the drug treatment.
Although the lymphangitic neoplasms in lymphangiomatosis are benign, the
disease process carries a poor prognosis, especially when there is pulmonary
involvement1,3,6,8,10.
The benign proliferation of lymphatic tissues seen in this entity are not
known to metastasize, but they can be extremely destructive
locally1,6,8,15,16.
The diagnosis of lymphangiomatosis is generally made during childhood or early
adulthood2,3,6,9,14,16.
The disease is thought to be congenital and only occasionally familial.
Females are more often affected than
males1,3,5.
Until relatively recently, treatment of lymphangiomatosis had been based on
the symptoms related to the swelling of a local site or impairment of
pulmonary
function1,3,6,18.
Spontaneous regression (two patients) and resolution after surgical treatment
(five of eleven patients) were reported by Dajee and
Woodhouse19.
However, such occurrences are rare.
Multiple treatment modalities have been used either systemically or locally
to control the disease, and most have had little effect. Radiation was used in
the past for local osseous or pulmonary disease with some
success7,13,18-21.
The dose of radiation required was approximately 20 Gy for chest lesions and
as much as 40 Gy for lesions in other areas of the
body7,20,21.
Corticosteroids2,3
and chlorambucil3
have also failed in the past.
The use of interferon-alpha was introduced because it was found to be
successful in the treatment of childhood hemangiomas. For those lesions as
well as for lymphangiomas, it is now considered to be an important regulator
of cell growth and
differentiation22-25.
Interferon-alpha is believed to have some antiproliferative and
anti-angiogenic properties, which seem to make it a reasonable choice for the
treatment of this
disorder17. There
are now multiple reports describing the use of interferon-alpha for the
treatment of patients with
lymphangiomatosis11,17,24,25.
Some of the reports described extremely ill patients with pulmonary
involvement who had correspondingly mixed results; but, clearly, as was seen
in our patient, the use of this agent can be quite effective in patients with
bone and soft-tissue
disease11,17,26.
At a follow-up visit five years after the start of interferon-alpha
therapy, our patient had an extremely good clinical response to treatment with
minimal toxicity. His quality of life had improved substantially. He looked
and felt well, and he had been able to attend college and participate in some
extracurricular activities.
The treatment of lymphangiomatosis of bone and the adjacent soft tissues
prior to the advent of interferon-alpha was a difficult orthopaedic problem,
as was seen in the present case. The multiple interventions described above
provided some relief of the symptoms, but the disease process is very
difficult to control. The addition of interferon-alpha changed the course for
our patient and should be tried for others with similar conditions. ?