Keywords
cystic angiomatosis - metastatic malignant lesions - bone lesions - PET-CT - case
report
Introduction
Cystic angiomatosis (CA) is a rare and benign pathological entity with uncertain etiology.[1]
[2] It is characterized by multifocal bony lesions affecting the axial and appendicular
skeleton, with possible visceral organ involvement.[3] CA is predominant in males and usually discovered at the age of puberty with a second
peak after 60 years.[4] Radiological imaging of this condition often resembles metastatic malignant lesions
and differential diagnosis is the key to differentiate it from other conditions. Treatment
is symptomatic and often a conservative approach appeared to be an appropriate option.
In the majority of patients, the disease is nonprogressive and outcomes are unpredictable.
Due to the rarity of the condition, literature related to this condition is limited.
Given this and to understand the condition better concerning differential diagnosis,
here we present a case of CA with bone lesions mimicking metastatic cancer.
Case Report
A 24-year-old female presented to our center with complaints of lower backache (∼4–6
weeks), intermittent pain in the abdomen, and occasional dyspnea on exertion. Ultrasound
showed mild splenomegaly with multiple small-sized cysts measuring 6 to 9 mm. Computed
tomography (CT) abdomen revealed multiple mild lytic lesions in the dorso-lumbar vertebrae,
sacrum, and both the iliac bones. Mild splenomegaly was observed measuring 158 mm
in span. Multiple varying sized cysts were reported in splenic parenchyma, with the
largest measuring 33 × 27 mm. The possibility of CA or multiple myeloma was inferred.
To confirm the condition, further immunofixation panel and whole-body positron emission
tomography-CT (PET-CT) scan were performed. The immunofixation panel has shown no
notable values. However, PET-CT has reported splenomegaly with extensive FDG (fluorodeoxyglucose)
non-avid cysts studded in the spleen ([Fig. 1A]). A well-defined, FDG non-avid, cystic/lytic lesions involving the right frontoparietal
bone and axial skeleton was also noted ([Fig. 1B, C]). Except for it, no other FDG avid lesions were reported, eliminating the possibility
of primary or distant metastasis ([Fig. 1]). The patient was advised for bone marrow aspiration and biopsy to complete the
diagnostic investigation, but the patient refused to undergo any further tests. Differential
diagnosis and reports from the tests are suggestive of CA. As a supportive treatment,
the patient was started on zoledronic acid (4 mg/intravenous [IV]) every 3 months
to stabilize the bone lesions. Along with zoledronic acid, cholecalciferol, calcium,
and vitamin D3 oral supplementation were provided. The patient is on follow-up and
regular PET-CT has shown no significant changes/new lesions in the past 2 years.
Fig. 1 PET-CT scan. (A) Splenomegaly noted with extensive FDG non-avid cyst studded in spleen. (B) FDG non-avid, lytic lesion involving right fronto-parietal bone was noted. (C) Multiple well-defined cystic/lytic lesions involving axial skeleton are all FDG
non-avid. FDG, fluorodeoxyglucose; PET-CT, positron emission tomography-computed tomography.
Discussion
CA was first reported by Parsons and Ebbs[5] in the 1940s and later by Jacobs and Kimmelstiel[6] in the early 1960s. Literature reiterated CA as a benign disease resembling malignant
lesions with a progressive course. In the present case report, the patient was young
and female. Literature suggests that CA is generally presented in the first few decades
of life, as reported in our patient. However, in some patients, its onset was reported
in their 60s and it was considered as a second frequency peak.[1]
[3]
[4] CA is predominant in males over females with a ratio of 3:2.[4] CA is asymptomatic in its early stages but with its progression, the clinical symptoms
such as pain in joints/spine, swelling, splenomegaly, scoliosis, and loss of strength
were prominently noted.[1]
Differential diagnosis of CA based on the clinical presentation itself is next to
impossible. CA shares features with Gorham–Stout disease (disappearing or vanishing
bone disease) and its multiple bone involvement also mimics multiple conditions such
as histiocytosis, Paget's disease, multiple myeloma, lymphoma, and bone metastases.[1]
[7] So, radiological imaging is the only option best advised to identify the typical
features of CA. The classical imaging features of CA as per literature are it should
be multifocal intramedullary skeletal cysts, oriented along the long axis of the bone,
and classically surrounded with a sclerotic peripheral ring with relatively well-preserved
cortical bone showing no periosteal reaction. CA is also a concomitant disease and
on imaging, involvement of multiple sites may be noted fortuitously. The most commonly
affected sites are bone, especially of femur (∼80%), and pelvis (∼73%).[3]
[4]
[7] Visceral involvement is reported in one-fourth of cases, especially spleen (∼25%
of cases), followed by skin, soft tissues, lungs, kidneys, etc.[1]
[2]
[3]
[4]
[7] The least expected sites are the tarsus, phalange, metacarpal, and carpal bones.[4] As reported in the literature, in our patient also we observed splenomegaly with
multiple mild lytic lesions in the dorso-lumbar vertebrae, sacrum, and iliac bones.
To date, no specific biological features have been reported related to CA. In recent
times, some authors have reported to observe alkaline phosphatase levels and cell-mediated
immunity (CD4 and CD8 T-cell lymphopenia).[4]
Post-imaging, biopsy from bone lesions or visceral lesions can be considered for histopathological
confirmation. In conditions like CA, histological diagnosis by performing a single
biopsy is often unrevealing and demands multiple bone biopsies to provide a concrete
diagnosis of the condition. On histopathology, the majority of the studies revealed
the tissue with CA will appear to have cystic walls with flattened, single layer of
endothelial cells. Furthermore, a significant proportion of the cellular structures
displayed vascular channels, cavities, spaces, canals, cysts, as well as features
characteristic of lymphangiomas and hemangiomas.[1]
[3]
[4] In our case, as the patient was unwilling to undergo a biopsy, CA was inferred based
on imaging findings and negative immunofixation panel, which ruled out multiple myeloma.
Treatment related to CA is always supportive and it is highly dependent on the symptoms.
At present, the reported treatment modalities from the literature include radiation,
surgery, interferon, steroids, calcitonin, propranolol, anti-VEGF (vascular endothelial
growth factor) or anti-VEGFR, and bisphosphonates.[8]
Considering all the treatment options, our patient was initiated on a preventive treatment
strategy, where we started our patient on zoledronic acid, 4 mg once every 6 months.
Zoledronic acid has been reported to modulate and control the migration/adhesion of
endothelial cells and the expression of angiogenic cytokines, which may probably stabilize
the bone lesions and prevent any skeletal events. Further, Najm et al[4] have reported the use of zoledronic acid and it resulted in stabilization of bone
lesions even after 2 to 4 years of use. In another study Marcucci et al,[9] an amino bisphosphonate therapy (pamidronate—30 mg IV every month) was adopted initially
for 2 years followed by zoledronic acid (5 mg/once a year) for the next 3 to 5 years.
At the end of the second year, improvement in bone mineral density was observed but
not up to the mark and such values are still compatible with osteoporosis. However,
no significant changes in the extent and size of the lytic areas were noted. By the
end of 5 to 7 years, a marked improvement in densitometric values with stable bone
lytic lesions was noted.[9] Given the extensive bone lesions in our patient, we decided to treat our patient
using zoledronic acid alone with complementary vitamin supplementation. To date, the
disease is stable and no new lesions have been noted. At the last follow-up visit,
the patient showed no signs of new symptoms and is set to return for follow-up evaluations
every 6 months. Inj. zoledronic acid was stopped after 2 years. From our observation
and clinical experience, we conclude that CA prognosis and clinical evolution are
strictly dependent on the extent of the disease and its severity, followed by its
treatment strategy.
Conclusion
Differential diagnosis of CA using various diagnostic techniques (radiological, pathological,
and laboratory investigations) at the earliest is highly recommended to rule out the
malignancy at an early stage to establish an accurate diagnosis. CA is also a heterogeneous,
self-limiting disease of unpredictable progression and uncertain treatment, where
often a conservative approach appears to be an appropriate option. In the future,
it is highly recommended to disseminate research findings of all such CA rare cases
to find out any new pathophysiological findings and to establish an effective treatment.
