The undifferentiated carcinoma that became a melanoma: Re-biopsy of a cancer of an unknown primary site: a case report.
BACKGROUND
Cancer of unknown primary site is still a demanding condition as it is per definition metastatic, with heterogeneous biological behavior, and it is often resistant to therapy. Cancer of unknown primary site accounts for approximately 1 to 5 % of all cancers, but is currently among the top six causes of cancer deaths in Western countries. To correctly identify the biological origin of the tumor, a large spectrum of differential diagnoses must be considered and scrutinized. At progression, re-biopsy might be necessary to reveal the true origin of the tumor or actionable targets.


METHODS
A 62-year-old Norwegian woman, with a fast growing lump in her left groin, was primarily diagnosed as having undifferentiated carcinoma that was BRAF V600 positive. There was complete response with paclitaxel-carboplatin and she was recurrence-free for 18 months. She had recurrence in both lungs and subcutaneously in her left groin and thigh; a re-biopsy revealed transformation to a malignant melanoma. She was resistant to BRAF inhibitors, then treated with ipilimumab and is currently a long-term survivor of 4 years and 4 months since the first diagnosis, with no clinical or radiological evidence of recurrence.


CONCLUSIONS
A biopsy from patients with metastasis of unknown primary should be analyzed thoroughly to identify organ of origin, molecular make-up, and possible molecular targets. Re-biopsy of cancer of unknown primary site at progression can reveal the true cellular origin of the tumor as well as provide novel therapeutic opportunities, including immunotherapy.
Cancer Clinic, Department of Surgery, Levanger Hospital, Nord-Trøndelag Hospital Trust, Kirkegata 2, N-7600, Levanger, Norway. oluf.roe@ntnu.no.|Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Prinsesse Kristinsgt. 1, N-7491, Trondheim, Norway. oluf.roe@ntnu.no.|Clinical Cancer Research Center, Department of Clinical Medicine, Aalborg University Hospital, Hobrovej 18-22, DK-9100, Aalborg, Denmark. oluf.roe@ntnu.no.
Oluf Dimitri
OD
Røe
Department of Pathology and Medical Genetics, St. Olavs Hospital, Erling Skjalgssons gt. 1, N-7491, Trondheim, Norway.
Sissel Gyrid Freim
SG
Wahl
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D005260:Female; D006119:Groin / Q000473:pathology*; D006801:Humans; D000074324:Ipilimumab; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy / Q000473:pathology*; D048493:Proto-Oncogene Proteins B-raf; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D013848:Thigh / Q000473:pathology*; D016896:Treatment Outcome; D000096142:Cutaneous Malignant Melanoma
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D048493:Proto-Oncogene Proteins B-raf
BRAF mutation; Cancer of unknown primary; Case report; Immunotherapy; Melanoma