Heterotopic ossification in lymph node metastasis after rectal cancer resection: a case report and literature review

• Published in: World journal of surgical oncology 2021-01, Vol.19 (1), p.2-2, Article 2
• Main Authors: Nagano, Hideki, Togawa, Tamotsu, Watanabe, Takeshi, Ohnishi, Kenji, Kimura, Toshihisa, Iida, Atsushi, Noriki, Sakon, Imamura, Yoshiaki, Sato, Yasunori, Goi, Takanori
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Aged, 80 and over; Antigens; Biomedical materials; BMP-2; Bone diseases; Brain; Brain cancer; Cancer; Cancer therapies; Care and treatment; Case Report; Case studies; CD56 antigen; CDX2 protein; Chemotherapy; Colorectal cancer; Development and progression; Diagnosis; Edema; Epithelial-mesenchymal transition; Female; Gastrointestinal tract; Heterotopic ossification; Humans; Lesions; Literature reviews; Lymph node; Lymph nodes; Lymphatic Metastasis; Lymphatic system; Mesenchyme; Metaplasia; Metastases; Metastasis; Necrosis; Nestin; Ossification (ectopic); Ossification, Heterotopic - etiology; Ossification, Heterotopic - surgery; Osteoblast-like cell; Osteoblasts; Osteocalcin; Osteonectin; Ostomy; Pathogenesis; Pluripotency; Pneumonia; Prognosis; Rectal cancer; Rectal Neoplasms - surgery; Rectum; Smad2 protein; Thyroid gland; Transforming growth factor-b1; Tumor cells; Tumors
• ISSN: 1477-7819; 1477-7819
• DOI: 10.1186/s12957-020-02098-x

Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear. An 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-β1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7. This is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.