Ready for the Unexpected

Dr Ben Kong

Investigating Patients with Suspected Malignancy

The incidental discovery of lesions during imaging for benign conditions in otherwise asymptomatic patients is a source of concern and frustration for patients and clinicians alike. Systematic reviews suggest that the prevalence of true malignancy in “incidentalomas” varies by organ, with breast lesions being malignant in around 42% of cases; renal, thyroid, ovarian lesions in around 25%, and prostatic in 10-20% of cases [1]. In some cases, a diagnosis is made from metastatic lesions without a primary, as observed occasionally in renal cell carcinoma and melanoma. In other cases, the diagnosis of cancer of unknown primary (CUP) must be made. This is the 5th most common cause of cancer death in men and 4th most common in women [2].

In most cases the initial evaluation of suspected malignancy will lead to identification of a primary lesion. Workup includes a complete history and physical examination, including directed breast, genitourinary, pelvic and/or rectal examinations, paying attention to past biopsies or imaging and spontaneously regressing lesions. History alone often suggests suitable sites for biopsy or further invasive investigation. Tumour markers are not routinely recommended as a screening tool for asymptomatic patients due to their lack of specificity. However they may be a useful adjunct in localising suspected malignancies or monitoring for treatment response.

Guidance on how to further investigate patients based on their histology and pattern of spread have been published by the US National Comprehensive Cancer Network (NCCN). A example of investigations to consider for patients with histological diagnosis of adenocarcinoma or carcinoma but no obvious primary site is shown in Table 1 below.

Table 1.

Clinical Presentation

Investigations to Consider

Supraclavicular fossa, axillary nodes

CT C/A/P, 

Women: Immunohistochemistry ER/PR/HER2, MMG/US, Men >40yo PSA


Serum b- HCG, a-fetoprotein, 

Men: Testicular US

Chest, pleural effusion, 

Women: CA125


Urine cytology + referral for cystoscopy

Serum CA 19-9 if pancreas of biliary suspected

Women: CA125

Retroperitoneal, liver

Serum b- HCG, a-fetoprotein

MenTesticular US


Consider referral for colonoscopy

Serum CA 19-9 if pancreas or biliary suspected


Bone scan

Table 1 – Suggested initial investigations for investigation of adenocarcinoma or carcinoma (not otherwise specified) in patients with suspected malignancy (adapted from [3]).

Neoadjuvant systemic therapy prior to surgery has an accepted role in locally advanced breast and gastrointestinal cancers, bladder cancer and gynaecological cancers. It is actively being investigated in other tumours such as kidney cancer, lung cancer and melanoma, therefore early involvement of multidisciplinary management is critical to coordinating the correct sequencing of treatments.


  1. O’Sullivan, JW, Grigg, S, Muntinga, T, Ioannidis, JPA, Prevalence and outcomes of incidental imaging findings: umbrella review, BMJ 2018.
  2. Australian Institute of Health and Welfare 2012. Cancer survival and prevalence in Australia: period estimates from 1982 to 2010. Cancer Series no. 69. Cat. no. CAN 65. Canberra: AIHW.
  3. NCCN Clinical Practice Guidelines in Oncology for Occult Primary, Journal of the National Comprehensive Cancer Network, 9(12), Dec 2011.

Dr Ben Kong

BSc(Hons), MBBS, FRACP (Medical Oncology)

Medical Oncologist with interests in genitourinary, lung and CNS tumours.

Locations: Mater Hospital, Sydney Medical Oncology


Phone: (02) 9911 7248

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Dr Ben Kong

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