True Trilineage Haematopoiesis in Excised Heterotopic Ossification from a Laparotomy Scar: Report of a Case and Literature Review

Abstract

We report a case of true trilineage haematopoiesis in an excised area of heterotopic ossification from an upper mid-line laparotomy scar. Heterotopic ossification is a rare complication of abdominal surgery and usually occurs when upper mid-line incisions are utilised. Whereas cases of heterotopic ossification in abdominal incisions are not exceedingly rare, true trilineage haematopoiesis in such an area of heterotopic ossification, to our knowledge, has only been previously reported once in the English literature.

Heterotopic ossification is a rare complication of abdominal surgery and usually occurs when upper mid-line incisions are utilised. Whereas cases of heterotopic ossification in abdominal incisions are not exceedingly rare, true trilineage haematopoiesis in such an area of heterotopic ossification, to our knowledge, has only been previously reported once in the English literature.

Case report

An 80-year-old man with a history of partial gastrectomy for a benign gastric ulcer in 1972 was referred to the gastroenterology clinic of University College Hospital for investigation of his anaemia, which was identified following an episode of collapse. He was otherwise asymptomatic with no history of abdominal pain, weight loss, change in bowel habit, malaena or bleeding per rectum. His past medical history included bilateral inguinal hernia repairs, a cerebrovascular accident, arterial hypertension, osteoporosis and non-metastatic prostate adenocarcinoma. He was on treatment for osteoporosis and hypertension and there were no allergies or any relevant family history. He was of Italian origin and did not smoke or consume alcohol.

Clinical examination revealed no peripheral stigmata of gastrointestinal disease other than a well-healed upper mid-line laparotomy scar. The vital observations were all within the normal limits; on palpation of the abdomen, there was a slightly tender, bony-hard mass located supra-umbilically in the mid-line scar that was not attached to the skin. There were no other tender areas in the abdomen and no muscle guarding, rebound tenderness or any other signs of peritonism. No other abdominal masses were detected and digital rectal examination revealed an enlarged prostate but no rectal masses, tenderness, blood or malaena.

A computed tomography (CT) pneumocolon scan was carried out which confirmed the presence of a mucosal lesion at the hepatic flexure of the colon, without any evidence of metastasis. Interestingly, the CT scan also confirmed the presence of a bony structure in the mid-line of the anterior abdominal wall with signal intensity of a ‘rib’ containing a bone marrow cavity (Fig. 1). A subsequent colonoscopy and biopsy confirmed the diagnosis of adenocarcinoma at the hepatic flexure of the colon and the patient was booked for an urgent laparotomy and right hemicolectomy.

Figure 1.

CT pneumocolon showing a bony structure in the mid-line of the anterior abdominal wall (arrow) with signal intensity of a ‘rib’ containing a bone marrow cavity.

A written, informed consent was obtained from the patient and a mid-line laparotomy and right hemicolectomy was carried out. Intra-operatively, a 10 cm × 2 cm bony structure resembling a rib was identified in the supra-umbilical incision scar between the peritoneum and the linea alba. This bony structure, which was not attached to the xiphoid process of the sternum, was excised and sent for histological examination. Figure 2 shows the macroscopic appearance of the excised specimen, while Figure 3 illustrates the histological appearance of the excised area of heterotopic ossification. A routine right hemicolectomy was subsequently carried out and the abdomen was closed with non-absorbable mass closure sutures and clips to the skin.

Figure 2.

The macroscopic appearance of the excised specimen.

Figure 3.

Histological appearance of the excised area of heterotopic ossification.

Following an uneventful recovery from the operation, the patient was discharged home, with an urgent follow-up appointment for discussion of the histology results and further management. Histology of the excised specimen from the anterior abdominal wall confirmed heterotopic ossification showing metaplastic bone formation that contained a marrow cavity with all three haematopoietic lineages of normal maturation.

Discussion

Heterotopic ossification is defined as the extraskeletal formation of lamellar bone and is a rare complication of abdominal surgery, seen more commonly in mid-line laparotomy wounds and especially following gastric and other upper gastrointestinal surgery. It is more common in males than females with a ratio of 5:1 and a mean age at presentation of 55 years.¹ Although there is still uncertainty about the aetiology of formation of this ectopic bone in abdominal incisions, it has been suggested that a probable cause is intra-operative injury to the xiphoid process of the sternum (or the pubis in lower mid-line incisions) leading to liberation in the wound of bone-forming cells.¹

Kaplan and co-workers² suggested that four factors are necessary for the development of heterotopic bone:

1. There must be an inciting event, such as an episode of trauma, which can be as trivial as a few torn muscle fibres.

2. An inductive signalling pathway is needed, most probably in the form of a protein secreted from the injured cells.

3. There must be a supply of mesenchymal cells whose genetic machinery is not fully committed. Under the appropriate signal, genes which synthesise osteoid and chondroid cells are activated, causing these mesenchymal cells to differentiate into osteoblasts and chondroblasts.

4. There must be an appropriate environment, which is conducive to the continued production of the heterotopic bone.

Even though little is known about the molecular pathogenesis of heterotopic ossification, research into fibrodysplasia ossificans progressiva, has provided new insights. Jaimo and co-workers³ studied the behaviour of bone morphogenetic proteins (BMPs) in fibrodysplasia ossificans progressiva and found an overexpression of BMP-4, which is a potent osteogenic morphogen. The effects of BMPs are highly regulated by negative feedback from the antagonists noggin, gremlin, follistatin and chordin. Underexpression of these antagonists results in reduced negative feedback which, in turn, leads to overexpression of BMP-4 and a subsequent increased differentiation of osteogenic cells.⁴

Important pathophysiological factors that contribute to the development of heterotopic ossification are tissue hypoxia, hypercalcaemia, changes in sympathetic nerve activity, prolonged immobilisation, mobilisation after prolonged immobilisation, and disequilibrium between calcitonin and parathyroid hormone.⁵ Injections of prostaglandin E₂ (PGE₂) in growing rats induce heterotopic bone formation and PGE₂ excretion in 24-h urine collections is a valuable indicator of early heterotopic ossification.⁶

Michelsson and Rauschning⁷ carried out an experimental study in rabbits consisting of hind limb immobilisation followed by repeated passive forcible exercising. Muscle necrosis occurred within a few days, followed by heterotopic cartilage and bone formation in the soft tissues around the joint within 2–5 weeks. The changes were morphologically and radiographically similar to those observed in human myositis ossificans and their incidence was correlated with the duration of immobilisation and the frequency of manipulation.⁷

Heterotopic ossification in abdominal scars, as in this case, can be asymptomatic and identified only incidentally on clinical examination or imaging of the abdomen for another condition. However, when symptomatic, it usually presents as a painful mass within the mid-line abdominal incision scar. Fractures of heterotopic ossification in abdominal scars have been reported in the literature but are a very rare mode of presentation.⁸ Traumatic perforation of intra-abdominal viscera by an area of heterotopic ossification within the abdominal scar has also been reported in the literature but is an extremely rare presentation.⁹ Plain radiography, CT and magnetic resonance imaging (MRI) have all been used to supplement clinical examination in the confirmation of the diagnosis of heterotopic ossification of the anterior abdominal wall.

Conservative management is all that is necessary when the condition is asymptomatic or only minimally symptomatic. Surgical excision is indicated when the heterotopic ossification causes significant pain or when complications such as fracture or visceral perforation ensue, and it should be wide enough to reduce the incidence of recurrence. Etidronate disodium has been used to prevent recurrence after excision of heterotopic ossification in spinal-cord injury patients.¹⁰

Wang et al.¹¹ reported a case of chronic abdominal pain caused by heterotopic ossification in the laparotomy scar of a woman who underwent gastric reduction surgery for the treatment of obesity. The excised specimen contained bone marrow showing histological evidence of normal trilineage haematopoiesis.

To our knowledge, our case is the second reported incident in the English literature of excised heterotopic ossification from abdominal scars containing bone marrow showing histological evidence of normal trilineage haematopoiesis.