Cholesterol granulomas are frequently described occurring in the temporal bone as a result of inflammatory ear disease.1
However, they are not exclusive to this location. An intraventricular cholesterol granuloma near the septum pellucidum thought to be secondary to remote head trauma from a motor vehicle collision was previously reported.2
Orbitofrontal cholesterol granulomas have been associated with trauma as miniscule as a bee sting,3
and have been shown to recur after incomplete excision.3–5
Some of these have been reported to exhibitc evidence of dysplasia of the adjacent bone, suggesting a pre-existing bony or vascular anomaly as a possible etiology.6
Renal cholesterol granulomas were thought to be associated in separate cases with hypercholesterolemia or atheromatous cholesterol emboli and epithelioid angiomyolipoma.7,8
In the breast, the inciting event was postulated to be duct ectasia or periductal inflammation.9
Previously reported anterior mediastinal cholesterol granulomas have been associated with prior trauma and multilocular thymic cyst.2,10,11
Pancreatic cholesterol granuloma with peritoneal dissemination has been observed and may have been due to prior episodes of acute pancreatitis.12
There has been a case of multiple cholesterol granulomas associated with multiple endocrine neoplasia type-1, thought to be caused by systemic distribution of pancreatic enzymes.13
Regarding the general theory of the pathogenesis of these lesions, the prevailing wisdom believes that a traumatic or inflammatory event incites tissue hemorrhage. Subsequent erythrocyte degeneration, coupled with a local milieu of inflammatory cytokines, attracts immune cells to the region. Cholesterol from the destroyed cell membranes forms crystalline complexes which provoke a foreign-body giant-cell reaction.14
This process can result in a slow-growing mass which has the potential to be locally aggressive.2
Hyperlipidemia, cholesterol emboli, and impaired lymphatic drainage may also play a role in the formation of these lesions.7,10
Osseous metaplasia is an extremely rare and pathogenically mysterious feature of cholesterol granulomas that has been reported only twice before in the literature: in the breast and fallopian tube.9,15
It is theorized to be the result of pluripotent cell, mesenchymal cell, and fibroblastic differentiation into osteoblasts due to stimulation by pro-inflammatory cytokines such as interleukins and transforming-growth-factor-beta, and bone morphogenetic proteins.16–18
In the case of our patient, the remote motor vehicle collision that he had experienced in decades prior likely caused hemorrhage of anterior mediastinal soft tissues. The subsequent inflammatory response and erythrocyte breakdown stimulated a foreign-body giant-cell reaction to the cholesterol crystals formed from the plasma membranes of the degenerated cells. Though not entirely explainable, the environment within the area of the cholesterol granuloma encouraged the development of mature osteoid. Another less likely possibility is that small fragments of bone became lodged in the anterior mediastinum after the patient's major traumatic incident.
The differential diagnosis for anterior mediastinal masses as in this case include germ cell tumors, thyroid goiters or neoplasms, hemangiomas, and thymic lesions including cysts, thymoma, and thymic seminoma.19
Microscopically there were no ectodermal or endodermal elements present, nor were there any areas consistent with germ cell tumor morphology. The lesion did not have the vascular network expected in a hemangioma. Thymic or thyroidal tissue was not observed, but given the patients advanced age and expected thymic involution, a pre-existing thymic lesion could not be ruled out.
The imaging findings of these masses are not specific to cholesterol granuloma and may simulate different entities, both baleful and benign. Such mimics include dermoid cyst,6
pancreatic cystic neoplasm,12
renal cell carcinoma,8
and invasive thymic neoplasm.14
The unfortunate consequence of this is that unnecessary, potentially harmful interventions could be performed for this ultimately benign entity.14
In the cases of cholesterol granulomas that are causing clinical symptoms, surgical excision is the treatment of choice.