Abstract
BackgroundHeterotopic 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.Case presentationAn 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.ConclusionThis 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.
Highlights
Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton
There are a few reports of HO lesions in sites of recurrence, such as the lungs or laparotomy sites [3, 9], HO in metachronous metastatic lymph nodes from rectal carcinoma has not been reported in the English literature, to the best of our knowledge
Goswami [2] reported a case in which a metastatic lymph node with HO was simultaneously dissected with the primary rectal carcinoma lesion, which was without HO
Summary
Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. Heterotopic ossification (HO) is bone tissue formation outside the skeleton; the lesion may be benign or malignant [1, 2] This phenomenon has been reported in tumors of various organs, including the lung, breast, thyroid, parotid, pancreas, liver, and kidney [3,4,5,6,7]. The presence of HO lesions in both primary rectal cancer and metastatic lymph nodes has been reported in only one case [8]. We report a case of HO in a metachronous metastatic lymph node in the right axillary region after curative surgery for rectal cancer without HO and treatment by gammaknife therapy for metachronous brain metastasis without HO. The purpose of this article is to highlight the histopathological and immunohistochemical findings of HO in the metastatic lymph node and consider the pathogenesis of HO in the present case
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