VCOM Carolinas Research Day 2023

Clinical Case-Based Reports

Metastatic Chordoma to the Liver: A Case Report Ashley Harvey 1 , Peter Botrous 1 , Robert Palmer 2 , Jacob Vandersteenhoven 2 , Laura Spruill 2 , Jailan Osman 1 Dorn VAMC, Columbia, SC 1 , Lexington Medical Center, West Columbia, SC 2

Abstract # CBR-1




References This was a case report of a 77-year -old white male with a history of deep vein thrombosis, pulmonary embolism, peripheral neuropathy, and hypertension who originally presented with a sacral chordoma that was surgically excised and treated with adjuvant radiation therapy. After several years, the sacral tumor recurred and was treated with palliative radiation and chemotherapy. The recurrent tumor eventually metastasized to the liver and the patient was treated with pain control and chemotherapy. Currently, surgery and radiation are the most effective treatment for chordomas 5 . However, even with negative margins after surgery there is a high rate of local recurrence 1 . New chemotherapeutic medications are targeting specific genetic mutations within cancers to decrease adverse effects and increase efficacy of the medication. Unfortunately, there are no clinically significant genetic mutations in the liver lesions found in this patient. However, mutations were found in genes: AXIN1, CD70, CDKN2A/B, PTCH1, SPEN which have potential to become targets for chemotherapy in the future. The molecular analysis also showed microsatellite stability and a low tumor mutation burden, which means the patient’s treatment is effective in preventing new mutations and excess cell replication. In other patients, Cetuximab and Gefitinib were used to prevent growth of a recurrent sacral tumor and metastatic pulmonary lesions 14 . Another case study found a 30% reduction in tumor load of a patient treated with Pembrolizumab, a PD-L1inhibitor 15 . Multiple studies have shown Epidermal Growth Factor Receptor (EGFR) inhibitors such as Sapitinib, Gefitinib, and Erlotinib to be effective in preventing further tumor growth in several patients 16 . Unfortunately, this patient’s liver metastases are negative for EGFR and therefore would not respond to these treatments. As previously stated, the patient is currently taking Erlotinib and reports pain relief, but imaging shows little effect on tumor size. Further research is warranted on how targeted chemotherapeutic agents can be used to more effectively treat chordomas and prevent recurrence and metastases. This case is noteworthy, because chordomas are unusual tumors with an incidence rate of 0.08 per 100,000 1 and there have only been 8 reported cases of liver metastases in the literature 1 . This case report serves to increase awareness of chordomas, how to identify them using microscopic and immunohistochemistry, and treatment. 1. Dickerson, T.E.; Ullah, A.; Saineni, S.; Sultan, S.; Sama, S.; Ghleilib, I.; Patel, N.G.; Elhelf, I.A.; Karim, N.A. Recurrent Metastatic Chordoma to the Liver: A Case Report and Review of the Literature. Curr. Oncol. 2022, 29, 4625-4631. 2. Reith, J.D.; Perry, A.; Rosenblum, M.K.; et al. (2018). Rosai and Ackerman’s Surgical Pathology (11th edition), (pp. 1749, 2048, 1778 1779). Elsevier. 3. Young, V.A.; Curtis, K.M.; Temple, H.T.; Eismont, F.J.; Delaney, T.F.; Hornicek, F.J. Characteristics and patterns of metastatic dis-ease from chordoma. Sarcoma 2015, 2015 . 4. Tavernaraki, A.; Andriotis, E.; Moutaftsis, E.; Attard, A.; Liodantonaki, P.; Stasinopoulou, M. Isolated liver metastasis from sacral chordoma. Case report and review of the literature. J. Balk. Union Oncol. 2003, 8 , 381 – 383. 5. McMaster, M.L.; Goldstein, A.M.; Bromley, C.M.; Ishibe, N.; Parry, D.M. Chordoma: Incidence and survival patterns in the United States, 1973 – 1995. Cancer Causes Control 2001, 12, 1 – 11. 6. Sun, I.; Guduk, M.; Gucyetmez, B.; Yapicier, O.; Pamir, M. Chordoma: Immunohistochemical analysis of brachyury. Turk. Neurosurg. 2016, 28 , 174 – 178. Denaro, L.; Berton, A.; Ciuffreda, M.; Loppini, M.; Candela, V.; Brandi, M.L.; Longo, U.G. Surgical management of chordoma: A systematic review. J. Spinal Cord Med. 2018, 43 , 797 – 812. Hruban, R.H., Traganos, F., Reuter, V.E., Huvos, A.G. Chordomas with malignant spindle cell components. A DNA flow cytometric and immunohistochemical study with histogenetic implications. Am J Pathol. 1990, 137, 435-447. Manasan, C.V., Carnate, J. Dedifferentiated chordoma in a 53-year-old female, Philippine J of Pathol . 2018, 3. 12-15. Hruban, R.H., May, M., Marcove, R.C., Huvos, A.G. Lumbo-Sacral chordoma with high grade malignant cartilaginous and spindle cell components. Am J surg Pathol . 1990, 14. 384-389. Hung, Y.P., Diaz-Perez, J.A., Cote, G.M., Wejde, J., Schwab, J.H., Nardi, V., Chebib, I.A., Deshpande, V., Selig, M.K., Bredella, M.A., Rosenberg, A.E., Nielsen, G.P. Dedifferentiated chordoma: Clinicopathologic and molecular characteristics with integrative analysis. Am J Surg Pathol. 2020, 44. 1213-1223. Heffelfinger M.J., Dahlin, D.C., MacCarty, C.S., Beabout, J.W. Chordomas and cartilaginous tumors at the skull base. Cancer . 1973, 32. 410-420. Brooks, J.J. The significance of double phenotypic patterns and markers in human sarcomas: A new model of mesenchymal differentiation. Am J Pathol . 1986, 125. 113-123. Hof, H., Welzel, T., Debus, J. Effectiveness of Cetuximab/Gefitinib in the therapy of a sacral chordoma. Oncol. Res. Treat. 2006, 29. 572 574. Wu, X., Lin, X., Chen, Y., Kong, W., Xu, J., Yu, Z. Response of metastatic chordoma to the immune checkpoint inhibitor pembrolizumab: A case report. Front. Oncol . 2020, 10. 565845. Akhavan-Sigari, R., Gaab, M.R., Rohde, V., Abili, M, Ostertag, H. Expression of PDGFR-alpha, EGFR, and c-MET in spinal chordoma: A series of 52 patients. Anticancer Res . 2014, 34. 623-630. Meis JM, Giraldo AA. Chordoma. An immunohistochemical study of 20 cases. Arch Pathol Lab Med. 1988 May; 112(5):553-6. Wick MR, Burgess JH, Manivel JC. A reassessment of “chordoid sarcoma”. Ultrastructural and immunohistochemical comparison with chordoma and skeletal myxoid chondrosarcoma. Mod Pathol. 1988 Nov; 1(6):433-43. Rohatgi S, Ramaiya NH, Jagannathan JP, Howard SA, Shinagare AB, Krajewski KM. Metastatic Chordoma: Report of the two cases and review of the literature. Eurasian J Med . 2015 Jun; 47(2): 151-154. Kishimoto R, Omatsu T, Hasegawa A, Imai R, Kandatsu S, Kamada T. Imaging characteristics of metastatic chordoma. Japanese Journal of Radiology . 2012 May;30, 509-516

Chordomas are rare primary bone tumors originating from the notochord commonly arising in 40- to 60-year-olds. Chordomas most commonly arise in the sacrum of adults, but can also occur in the spheno-occipital region in children, or vertebrae of all ages. Chordomas grossly appear as lobulated, gelatinous, soft masses with areas of hemorrhage. Histologically they are separated into three categories: conventional showing polyhedral cells with abundant eosinophilic cytoplasm arranged in cords or nests called physaliferous cells embedded in mucinous matrix; chondroid characterized by cartilaginous components intermixed with physaliferous cells; and dedifferentiated or chordomas with spindle cell components that appear as biphasic on microscopy with nests of physaliferous cells among hypercellular spindle cells with distinct borders between the two types of cells. Immunohistochemistry shows positive Epithelial Membrane Antigen (EMA), S100, Cytokeratin 8 (CK8), Glial Fibrillary Acidic Protein (GFAP), and Brachyury staining. Up to 40% of patients have chordoma metastasis, most commonly to the lungs, bones, lymph nodes, and subcutaneous tissues. Metastasis to the liver is very rare and not well reported in the literature. This case report focuses on a 77-year-old patient with a history of sacral chordoma who presented for a recurrent lesion that had metastasized to the liver. He originally presented in May of 2013 complaining of back pain, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans showed a large destructive lesion of the sacrum. A Fine Needle Aspiration of the lesion was performed, samples were analyzed microscopically and stained with immunohistochemistry markers proving the mass to be a sacral chordoma. This lesion was treated with the standard treatment of surgical resection and adjuvant radiation therapy totaling 55.8Gray (Gy) in 31 fractions. In 2017 the patient returned complaining of back pain and leg numbness, MRI of his pelvis showed an enhancing lesion involving most of his remaining sacrum and left S1 nerve. The patient declined treatment at this time. Yearly imaging was done to monitor tumor size. In May of 2022 a CT scan of the patient’s abdomen and pelvis showed multiple lesions in his liver as well as destruction of the sacrum and paraspinal spread of the sacral mass. Microscopic analysis of samples from the sacral mass diagnosed the recurrence of his chordoma. Samples from the liver lesions were also microscopically analyzed, stained with immunohistochemistry markers, and sent for gene sequencing proving the lesions to be chordoma metastases of the liver. The patient opted for palliative radiotherapy at this time and received 37.5Gy in 15 fractions and Erlotinib to prevent further tumor growth. Further imaging has shown stable tumor size. A literature review done by Dickerson et al in 2022 found only eight other reported cases of chordoma liver metastases. Meaning, this is a rare case. This case report serves to increase awareness of chordomas, how to identify them using microscopic analysis and immunohistochemistry staining, and their treatment. In 2013 a 68-year -old white male with a history of deep vein thrombosis, pulmonary embolism, peripheral neuropathy, and hypertension presented to an outside facility with the primary concern of back pain for the past year that the patient stated was worse at night and relieved by walking. The patient also presented with bowel and bladder incontinence he stated had been occurring for the past nine months. CT and MRI scans of his pelvis showed a large destructive lesion slightly left of midline spanning from S2 to below the coccyx as seen in Figure 1. Fine needle aspiration of the mass revealed atypical cells with eosinophilic cytoplasm called physaliphorous cells indicative of a sacral chordoma. In May of 2013 the patient underwent surgical resection of the mass which included S1-S2 laminectomy, en bloc mass resection, sacrotomy, mesh bolster of the rectum, and adjuvant radiation therapy totaling 55.8Gy in 31 fractions. Surgical excision and radiation are the standard treatment for sacral chordomas 5 . Histologic analysis of the mass which measured 13cm by 9cm showed negative margins, 1x10 power mitotic rate and spindle cells among myocytes as seen in Figure 2. Immunohistochemistry staining of the mass is summarized in Table 1. The sacral mass stained positive for S100 and Brachyury supporting the diagnosis of Chordoma. In 2017 the patient returned with the primary concern of worsening back pain and numbness in his left leg for the past few months. MRI of his pelvis showed an enhancing mass measuring 7.1 cm by 4.6 cm by 5.4 cm that compressed the left S1 nerve and involved most of his remaining sacrum as seen in Figure 3. The patient decided to forego surgical or radiation treatment at this time, opting for Physical Therapy and pain control instead. Yearly MRIs were done to monitor the mass’s growth. In 2018 CT of the lumbar spine showed a new radiolytic lesion in L3. The patient underwent 37.5Gy in 15 fractions and started Erlotinib, a tyrosine kinase inhibitor, at this time for pain control. The patient reported improved pain and ambulation but reported continued numbness of his left leg and fecal incontinence. In 2020 a CT with contrast of the patient’s pelvis and abdomen showed the sacral mass had grown to 9.2cm by 6.9cm by 6.9cm with invasion of L5, the iliac bone, and the spinal canal from L5-S1. As well as an osteolytic lesion in L1 indicative of metastases 20 . The patient, now 75 years old, refused surgical or radiation treatment at this time, but continued Erlotinib because he stated it helped with the pain. In 2021 an MRI revealed worsening osseous destruction of the sacrum with paraspinal spread to the sacro-spinal canal and lumbo-sacral plexus. The patient reported worsening numbness of his left leg and back pain, but still denied surgical excision or radiation therapy. In May of 2022, a CT scan of the abdomen and pelvis showed the addition of large metastatic lesions in the liver as seen in Figure 4. Fine needle aspiration of these lesions showed spindle cells with nuclear pleomorphism and cytoplasmic variation in a myxoid background. Immunohistochemistry results summarized in Table 1 show positive staining for CK8, CK18, EMA, vimentin, and S100 all consistent with metastatic chordoma 17 . Molecular studies are summarized in Table 2 comparing the metastatic lesions to known chordomas 6 . The now 77-year-old patient refused surgery at this time and opted for palliative radiotherapy and pain management. After receiving 37.5Gy in 15 fractions the patient continued Erlotinib which he reports has eased his pain, but imaging shows has little effect on tumor size. The most recent CT from July of 2022 shows focal cystic/necrotic lesions in the left and right lobes of the liver and a bony destructive lesion of the lumbosacral junction, left posterior iliac bone, and left posterior acetabulum. Overall, the patient was treated with the standard of care and unfortunately his tumor recurred and metastasized. Case Presentation

Figure 1: MRI of original sacral mass

40x H&E

3x H&E

Figure 2 MRI of sacral mass

Figure 2: Sacral Chordoma at 3x and 40x. Spindle cells admixed with myocytes can be seen as well as a 1x10 power mitotic rate and negative margins.

Figure 1 Sacral Chordoma at 40x

Figure 1 Sacral Chordoma among at 3x


Figure 3: MRI of enhancing mass involving most of the remaining sacrum

Figure 4: CT of abdomen and pelvis with contrast from 5/19/2022 showing liver lesions

Table 2: Summary of Molecular Studies



CHORDOMAS 6 EGFR ‘•‹–‹˜‡ ‡‰ƒ–‹˜‡ PD-L1 ‘•‹–‹˜‡ ‡‰ƒ–‹˜‡ PDGFR ˜‡”‡š’”‡••‹‘ ‡‰ƒ–‹˜‡ KIT ˜‡”‡š’”‡••‹‘ ‡‰ƒ–‹˜‡ STAT3 ˜‡”‡š’”‡••‹‘ ‡‰ƒ–‹˜‡ AXIN1 ‡‰ƒ–‹˜‡ ‘•‹–‹˜‡ CD70 ‡‰ƒ–‹˜‡ ‘•‹–‹˜‡ CDKN2 A/B ‡‰ƒ–‹˜‡ ‘•‹–‹˜‡ PTCH1 ‡‰ƒ–‹˜‡ ‘•‹–‹˜‡ SPEN ‡‰ƒ–‹˜‡ ‘•‹–‹˜‡

Figure 4

Table 1: Summary of Immunohistochemistry


Original Sacral Mass

Liver Metastases

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Special thanks to Ms. Terri Hutchinson, RN


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