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A case of occult intrahepatic cholangiocarcinoma diagnosed by autopsy


Cancer of unknown primary is associated with unknown biology and dismal prognosis. The most common primary sites of cancer of unknown primary were usually the lungs in autopsy studies, and intrahepatic cholangiocarcinoma is rare. We describe the case of a 57-year-old male patient with systemic lymph node metastasis. Imaging examination failed to reveal primary cancer; however, immunostaining of cytokeratins 7, 19, and 20 of a metastatic axillary lymph node suggested a pancreaticobiliary cancer as a primary lesion. He died of liver abscess and sepsis, and then, autopsy indicated occult intrahepatic cholangiocarcinoma. We discuss the clinical course of this rare cholangiocarcinoma including the diagnostic procedure and also present a review of the English literature regarding patients with cancer of unknown primary.


Carcinomas of unknown primary (CUP) represent a group of heterogeneous tumors that has no identifiable origin [1]. Despite advances in tumor pathology and imaging techniques, such as positron emission tomography (PET), CUP account for about 5 % of all cancers [24] and are associated with a dismal prognosis [58]. In such CUP cases, an autopsy is performed to find the primary site.

In this report, we describe the case of a 59-year-old male patient with CUP. The patient was diagnosed with occult intrahepatic cholangiocarcinoma by autopsy. We present a review of the English literature regarding patients with cancer of unknown primary and discuss the clinical course and diagnostic examination for this occult cholangiocarcinoma case.

Case presentation

A 57-year-old male was investigated because of elevation of tumor markers (carcinoembryonic antigen (CEA) 12.9 mg/ml, carbohydrate antigen 19-9 (CA19-9) 658.5 U/ml). Enhanced computed tomography (CT) (Fig. 1a) and PET-CT (Fig. 1b) and endoscopy failed to detect a suspected primary lesion. As CT revealed multiple swollen abdominal (Fig. 1c) and axillary lymph nodes (Fig. 2a), an excisional biopsy of an axillary lymph node was performed. The histological diagnosis of the lymph node was a metastasis of adenocarcinoma (Fig. 2b). Because immunohistochemistry of the lymph node for cytokeratin (CK) 7 (Fig. 2c) and CK19 was positive and that for CK20 was almost negative (Fig. 2d), pancreaticobiliary cancer was suspected as primary lesion. Then, endoscopic retrograde cholangiopancreatography (ERCP) was performed; nevertheless, the primary lesion was not discovered. Biopsy from epithelium of the bile duct was obtained during ERCP, and the malignant cell was not found. Combination chemotherapy of gemcitabine and cisplatin was introduced; however, his disease had progressed. The patient died of liver abscess and sepsis 10 months after the introduction of chemotherapy. All diagnostic modalities which the patient underwent to obtain a diagnosis are listed in Table 1.

Fig. 1
figure 1

Enhanced CT and PET-CT. CT (a) and PET-CT (b) failed to detect the tumor in the liver. CT revealed multiple swollen abdominal lymph nodes (arrows) (c)

Fig. 2
figure 2

An excisional biopsy of axillary lymph node. CT (a) detected a swollen axillary lymph node (arrow) and an excisional biopsy was performed. The histological diagnosis of the lymph node was a metastasis of adenocarcinoma (b). Immunohistochemistry for CK7 was positive (c) and that for CK20 was almost negative (d). Bar 10 μm

Table 1 Diagnostic modalities which the patient underwent to obtain a diagnosis

Autopsy was performed to find the primary lesion. Macroscopically, a gray-white colored, ill-defined solid tumor in the lateral segment of the liver was found, invading the diaphragm (Fig. 3a). Pathological diagnosis was intrahepatic cholangiocarcinoma (Fig. 3b). Immunohistochemistry revealed that these tumor cells were positive for CK7 (Fig. 3c) and CK19 and were negative for CK20 (Fig. 3d), as well as axillary lymph node metastasis.

Fig. 3
figure 3

Postmortem findings. Macroscopically, a solid tumor (arrowheads) in the lateral segment of the liver was discovered (a). At histology, intrahepatic cholangiocarcinoma was observed (b). Immunohistochemistry of the lymph node for CK7 (c) and CK20 (d) was similar. Bar 10 μm

We reviewed recent English literature regarding patients with CUP [912] (Table 2). The most common pathology of CUP was adenocarcinoma, and the most common primary sites found by autopsy were usually the lungs followed by the pancreas. The possible reason why the lung is the common primary site in CUP is that small cell carcinoma is likely to develop metastasis even in its early stages [13]. However, we are not aware of similar cases with intrahepatic cholangiocarcinoma. The advantages of an autopsy in such cases are to identify the primary site, to provide closure for family members, and to correlate findings with antemortem investigations [9, 14, 15], in spite of the damaging disadvantage of the body. Autopsy can still play an important role, especially the problem-oriented autopsy in which a clinician provides clinical diagnoses and raises a specific question to be answered by the pathologist, like the present case [16, 17].

Table 2 Recent literature summary of studies of patients with cancer of unknown primary

The reason why we failed to detect this intrahepatic cholangiocarcinoma using many imaging modalities is considered as follows. Because cardiac pulsation can interfere with diagnostic imaging, it may be difficult to detect the solid tumor in the subphrenic area of the lateral segment of the liver. This area should be considered as one of the blind spots of imaging examination. There were no abnormal findings which could indicate the existence of the cancer lesion from the retrospective viewpoints. If an exploratory laparoscopy was performed, we might have found this intrahepatic cholangiocarcinoma. The result of the immunohistochemistry of the axillary lymph node was accurate in this case, so the treatment choice of chemotherapy with gemcitabine and cisplatin was adequate.


Despite advances in diagnostic imaging technology, identifying the primary sites in patients with metastatic malignancies is sometimes difficult even now. In the presented case, immunohistochemistry was accurate and useful, and exploratory laparoscopy may play a significant role to detect the primary lesion. Thus, various examinations should be performed for CUP patients to receive sufficient treatment.


Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.



carbohydrate antigen 19-9


carcinoembryonic antigen


endoscopic retrograde cholangiopancreatography


computed tomography


carcinomas of unknown primary


positron emission tomography


  1. Pentheroudakis G, Briasoulis E, Pavlidis N. Cancer of unknown primary site: missing primary or missing biology? Oncologist. 2007;12:418–25.

    Article  CAS  PubMed  Google Scholar 

  2. Tsuya A, Kurata T, Tamiya A, Okamoto I, Ueda S, Sakai D, Sugimoto N, Matsumoto K, Goto I, Yamamoto N, Fukuoka M, Nakagawa K. A phase II study of cisplatin /S-1 in patients with carcinomas of unknown primary site. Invest New Drugs [Epub ahead of print].

  3. Hainsworth JD, Greco FA. Treatment of patients with cancer of an unknown primary site. N Engl J Med. 1993;329:257–63.

    Article  CAS  PubMed  Google Scholar 

  4. Greco FA. Molecular diagnosis of the tissue of origin in cancer of unknown primary site: useful in patient management. Curr Treat Options Oncol. [Epub ahead of print].

  5. Randén M, Rutqvist LE, Johansson H. Cancer patients without a known primary: incidence and survival trends in Sweden 1960–2007. Acta Oncol. 2009;48:915–20.

    Article  PubMed  Google Scholar 

  6. Dova L, Pentheroudakis G, Georgiou I, Malamou-Mitsi V, Vartholomatos G, Fountzilas G, et al. Global profiling of EGFR gene mutation, amplification, regulation and tissue protein expression in unknown primary carcinomas: to target or not to target? Clin Exp Metastasis. 2007;24:79–86.

    Article  CAS  PubMed  Google Scholar 

  7. Thomassen I, Verhoeven RH, van Gestel YR, van de Wouw AJ, Lemmens VE, de Hingh IH. Population-based incidence, treatment and survival of patients with peritoneal metastases of unknown origin. Eur J Cancer [Epub ahead of print].

  8. Riihimäki M, Hemminki A, Sundquist K, Hemminki K. Time trends in survival from cancer of unknown primary: small steps forward. Eur J Cancer. 2013;49:2403–10.

    Article  PubMed  Google Scholar 

  9. Al-Brahim N, Ross C, Carter B, Chorneyko K. The value of postmortem examination in cases of metastasis of unknown origin—20-year retrospective data from a tertiary care center. Ann Diagn Pathol. 2005;9:77–80.

    Article  PubMed  Google Scholar 

  10. Blaszyk H, Hartmann A, Bjornsson J. Cancer of unknown primary: clinicopathologic correlations. APMIS. 2003;111:1089–94.

    Article  PubMed  Google Scholar 

  11. Mayordomo JI, Guerra JM, Guijarro C, García-Prats MD, Gómez A, López-Brea M, et al. Neoplasms of unknown primary site: a clinicopathological study of autopsied patients. Tumori. 1993;79:321–4.

    CAS  PubMed  Google Scholar 

  12. Maiche AG. Cancer of unknown primary. A retrospective study based on 109 patients. Am J Clin Oncol. 1993;16:26–9.

    Article  CAS  PubMed  Google Scholar 

  13. Lobins R, Floyd J. Small cell carcinoma of unknown primary. Semin Oncol. 2007;34:39–42.

    Article  PubMed  Google Scholar 

  14. McPhee SJ. Maximizing the benefits of autopsy for clinicians and families. What needs to be done. Arch Pathol Lab Med. 1996;120:743–8.

    CAS  PubMed  Google Scholar 

  15. McPhee SJ. The autopsy. An antidote to misdiagnosis. Medicine. 1996;75:41–3.

    Article  CAS  PubMed  Google Scholar 

  16. Zarbo RJ, Baker PB, Howanitz PJ. The autopsy as a performance measurement tool—diagnostic discrepancies and unresolved clinical questions: a College of American Pathologists Q-Probes study of 2479 autopsies from 248 institutions. Arch Pathol Lab Med. 1999;123:191–8.

    CAS  PubMed  Google Scholar 

  17. Bayer-Garner IB, M Fink L, Lamps LW. Pathologists in a teaching institution assess the value of the autopsy. Arch Pathol Lab Med. 2002;126:442–7.

    PubMed  Google Scholar 

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Correspondence to Hideo Baba.

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Oda and Hashimoto prepared the manuscript. Shiomi and Ohnishi performed pathological examination and contributed by histological consideration. Hayashi and Chikamoto contributed by editing it. Takeya and Baba reviewed it and were responsible for the manuscript.

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Oda, E., Hashimoto, D., Shiomi, Y. et al. A case of occult intrahepatic cholangiocarcinoma diagnosed by autopsy. surg case rep 1, 101 (2015).

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