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On Being a Doctor |

The Scent of Cancer

David P. Steensma, MD
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From Dana-Farber Cancer Institute, Boston, MA 02115.

Corresponding Author: David P. Steensma, MD, Division of Hematologic Malignancies, Dana-Farber Cancer Institute, 44 Binney Street, Suite D1B30, Boston, MA 02115; e-mail, david_steensma@dfci.harvard.edu.

Ann Intern Med. 2010;153(3):206-207. doi:10.7326/0003-4819-153-3-201008030-00014
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Use your five senses … Learn to see, learn to hear, learn to feel, learn to smell, and know that by practice alone you can become expert.

—William Osler





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Detection of tumor site-specific volatiles
Posted on August 20, 2010
Marc P van der Schee
Academic Medical Centre Amsterdam
Conflict of Interest: None Declared

TO THE EDITOR: We strongly support the notion by David Steensma (1) that the analytic ability of noses is vastly underrated. The author rightfully raises the question: what does cancer actually smells like? (1) Smell, either as a biological sense or as a chemical analytical process is based upon pattern-recognition of complex mixtures of volatile organic compounds (2). In exhaled breath these volatiles are a product of both physiological and pathological metabolic pathways. As such a scent can indeed function as a diagnostic tool in differentiating health from disease.

The recent development of pattern-recognition analytical techniques based on electronic noses (3) (mimicking the mammalian nose (2)), gas- chromatography (4) and ion-mobillity spectrometry show the enormous potential of olfaction-based diagnosis in lung cancer. Interestingly, very recently it was shown that exhaled biomarker profiles could even discriminate lung-, breast-, colon- and prostate cancer (5). However, the exact origins of these cancerous volatiles remain to be established. They may originate from a systemic response to a developing neoplasm such as cachexia and increased oxidative stress. Other volatiles could arise from the micro-environment of the tumor itself through processes of necrosis, obstruction and effusion. The aim of a currently ongoing study in our lab is to capture volatile signatures produced locally by bronchial carcinomas.

In 11 patients with histologically confirmed lung cancer we used a bronchoscope to obtain air from the sub(segment) of the lung closest to the tumor. As control, the contra-lateral (sub)segment of the unaffected lung was sampled. Air samples were analyzed by a carbon nano-particle electronic nose system. Pattern-recognition analysis showed that the volatile molecular profiles differ significantly between the affected and contra-lateral segment in patients with lung cancer (p<0.01).

These data suggest that the tumor itself indeed has a specific scent that is emitted into the micro-environment of the developing neoplasm itself. Further characterisation of tumor-specific volatiles by artificial olfaction may re-introduce the sense of smell into modern day clinical practice. Indeed, using ones (electronic) nose can tell us tales worth knowing (1).

Reference List

(1) Steensma DP. The scent of cancer. Annals of Internal Medicine 2010; 206(7):153.

(2) Buck L, Axel R. A Novel Multigene Family May Encode Odorant Receptors - A Molecular-Basis for Odor Recognition. Cell 1991; 65(1):175- 187.

(3) Dragonieri S, Annema JT, Schot R, van der Schee MPC, Spanevello A, Carratu P et al. An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. Lung Cancer 2009; 64(2):166-170.

(4) Phillips M, Cataneo RN, Cummin ARC, Gagliardi AJ, Gleeson K, Greenberg J et al. Detection of lung cancer with volatile markers in the breath. Chest 2003; 123(6):2115-2123.

(5) Peng G, Hakim M, Broza YY, Billan S, Abdah-Bortnyak R, Kuten A et al. Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br J Cancer 2010; 103(4):542-555.

Conflict of Interest:

None declared

Posted on August 26, 2010
Robert E. Jackson, M.D.
Department of Internal Medicine, The Methodist Hospital Houston TX 77030-2724
Conflict of Interest: None Declared


I was intrigued by Dr. Steensma's article in ON BEING A DOCTOR "The Scent of Cancer" in the August 3, 2010 issue of Annals(1). While the sense of human smell is not as acute as other mammals due to our number of receptor cells (dogs: 220 million; humans 6 million)(2,3) we as physicians/scientists tend to rely on "data" more than Osler's entreaty to "Use the five senses..."

Thus, opportunity becomes fleeting and may delay diagnosis and perhaps precipitate mishap.For me, it is symbolic that the olfactory nerve is CRANIAL NERVE NO. I. It is considered an unusual nerve because(a)it is literally exposed to the outside world via the nose(b)it regenerates and(c) it is a first order neuron and projects directly onto the thalmus(4).

I am reminded of my patient with diabetes and hypertension who had undergone a coronary artery bypass graft semi-emergently following a myocardial infarction. I was out on vacation but when I returned several days later I visited him on an early Monday morning. I entered his darkened room at 6:30 AM where he and his daughter were quietly sleeping. I immediately smelled rotting flesh;there are few things that have this odor. His sternum and leg were fine. When I examined a previous intravenous site, it was clear that he had necrotizing fasciitis. A plastic surgeon performed several surgical interventions which saved his hand and arm.

How could every caregiver who had entered his room in the previous 24 hours not smelled his rotting flesh? He had a team of skilled physicians, residents, nurses and therapists in one of the best hospitals in the world! I suspect their noses DID smell his dying arm but their brains did not RECOGNIZE its meaning. The Art of Medicine was not lost but may have been temporarily misplaced.As Edward R. Murrow once said:"The obscure we see eventually. the completely obvious, it seems, takes longer." Dr. Steensma's excellent article should remind us all how essential it becomes that we continue to emphasize to our students, residents,and ourselves to utilize the five senses and "...know that by practice alone you can become expert."


1. Steensma, D.P. The Scent of Cancer ON BEING A DOCTOR. Ann.Intern Med. 2010;153:206-207

2. Correa, J.E. The Dog's Sense of Smell. Alabama Cooperative Extension System NEW July 2006 1-4.Accessed at www.aces.edu/pubs/docs/U/UNP-0066/UNP-0066.pdf

3.Jafek, B.W. Ultrastructure of Human Nasal Mucosa. Laryngoscope 1983;93:1576-1599

4. Goetz, C.G. Textbook of Clinical Neurology.Philadelphia,PA:2003.99 -112

Conflict of Interest:

None declared

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