This case study highlights medical calculators and analytics which can be instrumental in a physician’s clinical decision making process, especially when the diagnosis can be complicated due to the patient’s prior health conditions.

Mary is a 66-year-old retired nurse. Five years ago she had been diagnosed with an adenocarcinoma that involved her right pleural space. An extensive work-up to identify a primary location was negative, so it was classified as a metastatic adenocarcinoma of unknown primary site.

  • Prognostic Scores for Predicting Survival in Patients with Metastatic Carcinoma from an Unknown Primary SitePrognostic Scores for Predicting Survival in Patients with Metastatic Carcinoma from an Unknown Primary Site

She was placed on chemotherapy. However the tumor responded poorly to the agents selected. She had pleural fluid sent to Helomics Corporation, a laboratory that performs susceptibility testing on tumor cells. They were able to demonstrate resistance to the chemotherapeutic agents that she had been receiving, and made recommendations for an alternative regimen. On the new regimen the tumor regressed and only a couple small nodules could be found on follow-up imaging studies. These shrank and became stable in size, and they were thought to be fibrotic nodules. She felt fine and was able to resume many of her usual activities, including gardening.

A month ago she came in for a routine follow-up imaging scan. Her chest X-ray showed multiple abnormalities including hilar lymphadenopathy. A PET scan was ordered and this showed several hot spots including one in a rib. Surprisingly the previous tumor nodules were all negative on the scan.

Recurrent Adenocarcinoma? New Malignancy?

A presumptive diagnosis of recurrent cancer was made. But the findings did not quite fit. The possibility of a second neoplasm was considered. This included lung cancer but she had never smoked and had no known risk factors. No masses were seen within the lungs.

Although an endobronchial ultrasound (EBUS) guided biopsy was proposed, she requested mediastinoscopy so that several accessible lymph nodes could be obtained for study. The pathology report that came back on these lymph nodes showed granulomas with central necrosis. No sign of cancer was seen in any of the nodes. Special stains for fungi were negative.

Causes of Granulomatous Inflammation?

While PET scans can be very helpful, people sometimes forget that the scan can be nonspecific, only indicating metabolic activity.

  • False-Positive and False-Negative Findings for Lung Cancer Associated with Positron Emission Tomography (PET)False-Positive and False-Negative Findings for Lung Cancer Associated with Positron Emission Tomography (PET)

The hilar lymphadenopathy and granulomas raise the possibility of sarcoid. Sarcoid can be associated with several neoplastic disorders. However, the hallmark of sarcoidosis is a noncaseating granuloma. While central necrosis can be seen, it is not typical and so should prompt some caution in making a diagnosis of sarcoid.

  • Prognostic Factors for a Patient with SarcoidosisPrognostic Factors for a Patient with Sarcoidosis
  • Sarcoidosis Severity ScoresSarcoidosis Severity Scores

Special stains for fungi are insensitive and so a negative stain does not exclude a fungal infection.

The patient lives in an area where several deep fungal infections are endemic – Histoplasmosis, Blastomycosis and Sporotrichosis. She gives a history of spending much of her free time gardening in her yard. She would often break wooden branches over her bare knee and spent a lot of time tending to her roses. About 3 months before the current episode she noted some purplish-tan nodules on her left knee where she broke the branches. Several small nodules had come and gone since then, and she had noted a swelling in her knee but thought she was just getting old. She hadn’t made a connection between her garden work and the swelling.

She was referred to an infectious disease specialist for evaluation of her skin lesions and to exclude a deep fungal infection. The swelling indicates that she may have sporotrichosis, also known as Rose Thorn Infection, a disease caused by the infection of the fungus Sporothrix schenckii.  Although this fungal disease usually affects the skin, it can also affect the lungs, joints, bones, and even the brain, if the fungal spores enter the body.  

  • Risk Factors Associated with Infections Caused by Sporothrix schenckiiRisk Factors Associated with Infections Caused by Sporothrix schenckii
  • Clinical Features of Disseminated Infection with Sporothrix schenckiiClinical Features of Disseminated Infection with Sporothrix schenckii


In a person with a history of cancer it is easy to jump to conclusions. However, it is necessary to adhere to a protocol to make the correct diagnosis. Medical algorithms can aid in clinical decision support. They can alert the clinician to discrepancies that may surface when determining a diagnosis and help to suggest alternative diagnoses.