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  IN THIS Article
 ::  Introduction
 ::  Material and methods
 ::  Case report
 ::  Discussion
 ::  Acknowledgement
 ::  References

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Year : 1985  |  Volume : 31  |  Issue : 2  |  Page : 118-20

Heterotopic (pathological) ossification (a report of 3 cases).

How to cite this article:
Kothare S N. Heterotopic (pathological) ossification (a report of 3 cases). J Postgrad Med 1985;31:118

How to cite this URL:
Kothare S N. Heterotopic (pathological) ossification (a report of 3 cases). J Postgrad Med [serial online] 1985 [cited 2023 Mar 28];31:118. Available from:

  ::   Introduction Top

Heterotopic ossification is defined as bone formation at the sites where normally ossification does not occur. This entity is now attracting the attention of histologists. Until lately, the study of this phenomenon was treated with indifference or overlooked as pointed out by Collins and Curran.[2]
Ossification in man is either of the endochondral (also known as intracartilagenous) or the intramembranous type. In the latter, the first bone to be formed is woven type. Such foci are the end result of woven bone formation following metaplasia in the mesenchymal cells or in dystrophic tissues with or without prior calcification. The well known examples are myositis ossificans, ossification in Ghon's lesion, in phthisis bulbi and in atheromatous plaques in aorta. However, there are several, lesser known sites such as bronchial cartilage, abdominal scar, laryngeal cartilage and calcifying epitheliomas where such ossification has been observed.[4],[6],[7],[8],[9],[11],[14],[15]

  ::   Material and methods Top

Representative portions of the specimens were taken, processed into paraffin block tissues and cut 6-7 u thick. Skip serial sections were stained routinely with hematoxylin and eosin, and alcian blue periodic acid Schiff (AB-PAS) combination,[10] to demonstrate acid and neutral mucopolysaccha-rides and the woven bone which is PAS positive. When necessary, sections were stained with Gomori's aldehyde-fuchsin and Masson's trichrome as a counter stain (GAF-MT) to identify sulfated mucopolysaccharides,[4],[13] and by the von Kossa technique to demonstrate calcium salts.[10]

  ::   Case report Top

Case 1:
A 51 year old Chinese female was admitted to the Sarawak General Hospital, for a lump in the left gluteal region of a few months' duration. There was a history of an injection at the same site several months ago. The excised specimen consisted of a mass of fibrofatty tissue, 4 x 2 x 2 cm in size. On sectioning, a cystic cavity, about one cm in diameter was seen in its substance. In the wall of the cavity, hard areas were felt. Histology showed changes consistent with dystrophic calcification and ossification.
Case 2:
A 25 year old Malay female was admitted with a lump in the right gluteal region since childhood. It had gradually increased in size but was not painful. There was no history of fever or loss of weight, nor any history of trauma or injection at the site in the past. During operation, one lipoma and two sebaceous cysts were excised. The specimen consisted of a mass of fibrofatty tissue, 4 x 5 x 8 cm in size, with the overlying elliptical skin. On sectioning through the mass, one large cavity, 6 x 5 cm in size, lobulated and containing a brown cheesy material was seen. Another smaller cavity with a smooth lining and a hard structure in its wall, was also detected. Histology of the larger cyst showed stratified squamous epithelium, lining the wall, ulcerated at places and replaced by granulation tissue infiltrated with giant cells and inflammatory cells. The histology was compatible with the diagnosis of an infected sebaceous cyst. A section through the smaller cyst showed well formed lamellar bone, surrounded by an adipose tissue. The histology was consistent with metaplastic ossification probably in the gluteal fat or in a lipoma [Fig. 1].
Case 3:
A 34 year old Malay female was admitted to the Miri General Hospital with a history of pain in the right iliac fossa since two years, and a mass of 6 months' duration. On examination, an intra-abdominal mass in the right iliac fossa was palpable. At operation, an ileo-caecal mass was detected and removed. The specimen consisted of the terminal part of the ileum and the caecum. In the paracaecal region, a cystic mass, 2.5 cm in diameter, with gelatinous material in the wall was seen. The appendix could not be identified. Coagulated gelatinous material (150 ml) was removed from the paracaecal region and examined. Histology from the cavity and the adjacent tissue showed the cavity lining composed of granulation tissue and basophilic staining mucin in H. & E. - stained sections. With the GAFMT stain, the mucin appeared purple in colour, indicating the presence of sulfated mucopolysaccharides. Besides this, narrow trabeculae of lamellar bone were also seen. The site and histology were compatible with the diagnosis of a mucocele probably of the appendix and metaplastic bone formation [Fig. 2].

  ::   Discussion Top

Case 2 is an example of mesenchymal metaplasia in tumours. Metaplastic bone formation in the connective tissue stroma of benign and malignant tumours has been observed.[15] Bone formation in benign mesenchymal tumours such as fibroma[6] and lipoma[12] has also been reported. Sood and Mudbhatkal,[12] on the basis of histochemical methods of staining, concluded that the reported osteochondroma originated by a metaplastic change in a lipoma. In Case 2 reported here, the bony foci appeared as islands in the adipose tissue and on correlating with the gross appearance, the histology was suggestive of ossification in a lipoma.
In Case 1, the history of a previous injection at the site was highly in favour of ossification in dystrophic tissue. In Case 3, the ossification appeared to be due to mesenchymal metaplasia following a mucocele of the appendix. Sulfated mucopolysaccharides were also demonstrated in the mutinous component of the inflammatory exudate. Juvera and Borcescu[5] reported a case of massive ossification in the necrotic debris associated with a ruptured mucocele of the appendix.
Sulfated mucopolysaccharides have been demonstrated in the epithelium of the gastro-intestinal tract, gall bladder and urinary bladder by Spicer and Meyer,[13] in bronchial mucous, bronchial mucous glands and in bronchial cartilages by deSouza and Kothare,[4] in close proximity of the newly formed bone in the laryngeal cartilages by Nirmala et al[11] and in the basophilic cells of calcifying epithelioma by Thomas and Kothare.[4] Heterotopic ossification has been observed in tumours of the gastro-intestinal tract, urinary bladder, hepatoma and the so-called mixed parotid tumour by Willis,[15] in bronchial cartilages by Kothare and deSouza[8] and in calcifying epithelioma by many authors.[7],[8],[9],[14] Is this association of sulphated mucopolysaccharides fortuitous or is the presence of such substances in tissues conducive to heterotopic ossification?
Bridges and Pritchard[1] have propounded that dying or dead cartilage cells, particularly the hypertrophied cells, liberate an inducer substance which may be responsible in the formation of heterotopic ossification. Recently, Cooney et al,[3] in their study on pulmonary carcinoid tumours, encountered ossification in 7 cases; in 4 of these, calcitonin was demonstrated in tumour cells in the viscinity of such ossification. They felt that locally produced calcitonin might be responsible for ossification of bronchial cartilages.

  ::   Acknowledgement Top

I am grateful to Dr. Tan Yaw Kwang, Director of Medical Services, Sarawak, for permitting me to report these cases, to the clinical staff for furnishing the relevant notes and the laboratory technicians for their co-operation.

  ::   References Top

1.Bridges, J. B. and Pritchard, J. J.: Bone and cartilage induction in the rabits. J. Anat., 92: 28-38, 1958.  Back to cited text no. 1    
2.Collins, D. H. and Curran, R. C.: Pathological ossification and osseous metaplasia in man: In, "Modern Trends in Pathology." Editor: D. H. Collins, Butterworth and Co. Ltd., London, 1959, pp. 300-334.   Back to cited text no. 2    
3.Cooney, T., Sweeney, E. C. and Luke, D.: Pulmonary carcinoid tumours; a comparative regional study. J. Clin. Pathol., 32: 1100-1109, 1979.  Back to cited text no. 3    
4.DeSouza, E. J. and Kothare, S. N.: The Gomori-aldehyde fuchsin stain in the study of sulfation, a histological study in human lung tissue. J. Postgrad. Med., 11: 165-168, 19,65.  Back to cited text no. 4    
5.Juvara, I. and Borcescu, U.: Heterotopic ossification of appendicular mucocele. Brit. Med. J., 1: 931-933, 1948.  Back to cited text no. 5    
6.Kothare, S. N.: Heterotopic ossification -case reports. Ind. J. Surg., 30: 154-159, 1968.  Back to cited text no. 6    
7.Kothare, S. N.: Pilomatrixoma (Calcifying epithelioma) in Sarawak-a report of 9 cases. Singapore Med. J., 22': 9698, 1981.  Back to cited text no. 7    
8.Kothare, S. N. and DeSouza, E. J. Changes in bronchial cartilages in diseased lungs and their relation to heterotopic ossification. Ind. J. Pathol. and Bacteriol., 8: 318-323, 1965.  Back to cited text no. 8    
9.Lever, W. F. and Schaunburgh-Liver, G.: In, "Histopathology of skin", 5th Edition, J. B. Lippincott Co., Philadelphia, London and Toronto, 1975.  Back to cited text no. 9    
10.Lillie, R. D.: In, "Histopathological Technique and Practical Histochemistry." 3rd edition, MacGraw Hill Book Company, New York, Toronto, Sidney, London, 1965.  Back to cited text no. 10    
11.Nirmala, P., Thomas, J. A. and Kothare, S. N.: Cancers of the larynx and hypopharynx, II-Laryngeal cartilage behaviour. J. Postgrad. Med., 20: 160-165, 1974.  Back to cited text no. 11    
12.Sood, I. D. and Mudbhatkal, Nalini, S.: Extraskeletal osteochondroma. Ind. J. Pathol. and Bacteriol., 10: 72-76, 1967.   Back to cited text no. 12    
13.Spicer, S. S. and Meyer, D. B.: Histochemical differentiation, of acid mucopolysaceharides by means of the combined aldehyde fuchsin-alcian blue stain. Amer. J. Clin. Pathol., 33: 435-460, 1960.   Back to cited text no. 13    
14.Thomas, J. A. and Kothare, S. N.: Calcifying epithelioma of Malherbe-a true tumour or a malformation? Ind. J. Cancer, 12: 179-186, 1975.  Back to cited text no. 14    
15.Willis, R. A.: "The Borderland of Embryology and Pathology." 2nd Edition; Butterworths and Co. Ltd., London, 1962, pp. 549-570.  Back to cited text no. 15    

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2004 - Journal of Postgraduate Medicine
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