Introduction

Necrotic areas of tumors often show dystrophic calcification, but mature bone formation also known as Osseous metaplasia or heterotopic bone formation is a rare phenomenon.

Osseous metaplasia refers to the formation of mature bone elements in the stroma of the neoplasm. This rare finding has been reported in both benign and malignant tumors of various organs.If malignant lesions only are to be considered osseous metaplasia has been observed mostly in adenocarcinomas occurring in the Gastrointestinal tract, lung, breast thyroid, parotid and pancreas ₁ . Very few cases of adenocarcinoma of the rectum with osseous metaplasia are reported in the literature.

Although osseous metaplasia is clinically and prognastically insignificant and most of the times it is an incidental microscopic finding, yet the presence of bone fragments in a malignant tumor should be evaluated carefully before labeling the lesion as osseous metaplasia.Not much is known about the pathogenesis of osseous metaplasia though there are some evidences indicating the role of Bone morphogenic proteins(BMP).

We present a case of adenocarcinoma of the rectum in an old lady with foci of osseous metaplasia and have reviewed the literature about osseous metaplasia in adenocarcinoma rectum.

Case Report

A 60 year old lady presented with bleeding per rectum and altered bowel habits of 2 months duration. The patient has lost weight recently. Routine investigations indicated iron deficiency anemia. Proctoscopy showed an irregular ulcerated mass in the rectum.

Preoperative CT Scan showed a 3X2 cms mass in the rectum invading the wall. Regional lymphnodes, adjacent viscera and liver did not show any sign of involvement. Anterio Posterior resection was performed and the tissue was sent for histopathological examination.

Gross appearance

Microscopic examination

Sections from the growth showed the typical features of mucin secreting and infiltrating adenocarcinoma of the rectum. The tumor tissue is seen invading the wall and reaching the serosa at places. All the lymphnodes examined showed only reactive hyperplasia.In the wall of the rectum where the tumor islands were seen invading, foci of osseous metaplasia were identified. These foci of mature bone were seen in the stroma surrounded by the tumor cells (Fig 1 and 2).

Figure 1

Figure 1: Low power view of Adeno carcinoma of the rectum with a focus of osseous metaplasia. H & E 10X

Figure 2

Figure 2: Higher power view showing the focus of osseous metaplasia with in a malignant glandular stroma.H & E 20 X

The tumor is seen mostly in the submucosa and at places invading through the muscularis propria.

In view of the presence of bony spicules with in the tumor the report was sent as Ossoeous metaplasia in well differentiated adenocarcinoma. The clinician was requested to look for direct invasion to pelvic bones. CT scan was done which did not show any evidence of tumor invasion of the adjacent pelvic bone.

Discussion

Osseous metaplasia or heterotopic bone formation in adenocarcinomas of the GIT is considered as a rare event. Very few cases are reported so far in the literature and it is mostly considered as histopathological curiosity ( Table)

Figure 3

Table 1: Published cases of osseouas metaplasia in colorectal carcinoma

Foci of ossification in rectal carcinoma was described by Dukes in 1939 for the first time in the English literature. The overall incidence of osseous metaplasia in malignant tumors is 0.4% approximately as suggested by Dukes ₉ .Ossification can occur in both neoplastic and non neoplastic lesions of the GIT like in colonic polyps,mucocele of the appendix,gastric carcinoids and adenocarcinomas ₅,₁₀,₁₁ .Osseous metaplasia is seen more commonly in lower gastrointestinal tract lesions with rectum being the most common site. However cases have been reported from sigmoid, transverse colon and caecum also ₈ .The average age of these patients was 56 yrs(range 36-72) and male to female ratio was 5:7 ₅ .Heterotopic bone formation is usually observed in tumors producing abundant mucin ₁₀ .It is speculated that the extravasation of mucin may have a stimulatory role in ossification ₁₂ .

Various studies have hypothesized that the Bone Morphogenic Proteins(BMP) play an I mportant role in osseous metaplasia in colonic adenocarcinoma. Rhone and Horowitz ₁₃ postulated that ossification might result from metaplasia of pluripotent mesenchymal cells into osteoblasts. Imai et al ₁₄ studied the immunohistochemical expression of BMP in colonic carcinomas and found that BMP-5 and BMP-6 were prominent in the cytoplasm of the tumor cells, but were weakly expressed in the osteoblast like cells adjacent to the nearby bone.BMP-2 and BMP-4 were strongly expressed in the surrounding mesenchymal cells and weakly expressed in the tumor cells and osteoblast like cells. This pattern suggests that the tumor cells mainly produce BMP-5 and BMP-6 which may induce proliferation of surrounding mesenchymal cells into preosteoblast and osteoblast expressing BMP-2 and BMP-4.(12).BMP-2 and BMP-4 are potent inducers of osteoblastic differentiation when compared with other BMPs ₁₅ .

Conclusion

Osseous metaplasia which is a very rare phenomenon may occur in both benign and malignant lesions of the GIT.The course and prognosis of adenocarcinoma with osseous metaplasia does not differ from that of adenocarcinoma without osseous metaplasia.Most of the times osseous metaplasia is an incidental finding on microscopic examination.Whenever mature bone fragments are found in the tumor tissue osseous metaplasia should be considered only after excluding invasion of adjacent bony tissue to the organ.The exact mechanism of osseous metaplasia is not known , but the recent evidences point out the role of BMPs.