Laura

| January 10, 2016

Laura was an active 29-year old mother of 2 who presented to her primary care provider with complaints of right hip pain. Following a physical examination she was provided some pain medications and referral to physical therapy. The pain persisted after several weeks of anti-inflammatory therapy, physical therapy and reduced exercise. At this point an MRI of the hip was ordered demonstrating a large mass in the right pelvis/hip. A fine needle aspiration/core biopsy of this pelvic mass showed a poorly differentiated carcinoma. Further evaluation demonstrated additional lung masses and subsequent fine needle aspiration/core biopsy of one of these lesions also showed a poorly differentiated carcinoma.

Tumor specific immunohistochemical stains peformed on the hip and lung masses were non-specific for a particular primary site of disease. Numerous tumor stains for lung, breast, gastrointestinal and renal cancers were performed repeatedly. The only consistent staining demonstrated as for HER2 on both the hip and lung mass. Armed with this information Laura was treated as “metastatic breast cancer” despite not having any detectable breast masses on repeated imaging studies with mammography, breast MRI and ultrasound.

Conventional chemotherapy for breast along with Herceptin was prescribed for Laura. After several months, subsequent imaging showed that the hip and lung masses had not significantly decreased in size and perhaps the lung masses had grown slightly.

I was asked by a friend of the family to review her slides. It was hard to argue with any of the pathology reports and work-up performed at a top-tier cancer center. I asked my oncologists to have her case presented at our tumor board for additional ideas after speaking with Laura’s oncologist and both Laura’s and her oncologist consent to do so.

After review of the slides and tumor board discussion we essentially reached the same conclusion that this was a poorly differentiated carcinoma but we felt that a breast primary was unlikely given her clinical presentation. Other primary sites such as lung with metastases to hip, or a gastrointestinal or renal primary were also thought less likely.

While not 100% certain, I was concerned the primary site could be gynecologic in origin, such as ovarian with direct extension into the hip/pelvis and with metastases to lung. Or perhaps a metastatic carcinoma of unknown primary.

Despite advances and increasing sophistication in the diagnostic workup for malignancies, detailed investigations fail to reveal a primary site of origin for a subset of patients with metastatic cancer. This is often referred to as carcinoma of unknown primary origin (CUP) or occult primary malignancy. The American Cancer Society estimates that more than 32,000 persons are diagnosed with CUPs annually. This would suggest that cancer of unknown primary origin constitutes about 2% of all cancers diagnosed in the United States. However, deaths due to cancer of unknown primary site were estimated to be over 45,000. This discrepancy between incidence and mortality is believed to be due to a lack of specificity in the listing of cause of death on death certificates.

The exact incidence of cancer of unknown primary origin in the United States is not precisely known. It is almost certainly underreported, and its true incidence is most probably between 2% and 6%. In 15-25% of cases, the primary site cannot be identified even on postmortem examination. The inability to identify a primary site of cancer poses many challenges. The primary site of cancer usually dictates the treatment, expected outcome, and overall prognosis.

Cancers are thought to arise from a single cell that escapes the controls of normal cell replication, forms a tumor at the site of origin, and ultimately metastasizes to other organs. In some cases, the original tumor may remain small or undetectable at the time of metastasis, leading to the clinical presentation of cancer of unknown primary origin. Whether a specific genetic or mutational factor plays a role in cancer of unknown primary origin remains uncertain.

As luck would have it, Laura’s oncologist would be attending ASCO and we could meet in person to discuss her case. He was perplexed, as were others he referred Laura to at another prominent cancer center.

Despite her tumor cells being “HER2 positive” she did not respond to Herceptin therapy, and actually her disease had progressed. Adding additional chemotherapy agents to cover a broader range of malignancies failed to control her disease.

Ultimately, he started Laura on regimens of chemotherapy for ovarian cancer with some detectable changes in the size of her tumors through the summer and fall until these therapies too failed and her lung masses grew significantly.

By Thanksgiving, Laura decided to go into hospice and forego any additional therapy.

Laura passed away earlier this year.

Hopefully someday we can eliminate trying to treat what we do not know. Primary tumors so small with large burdens of metastatic disease that evade our advanced imaging, immunohistochemistry, molecular and personalized cancer therapies.

For Laura and thousands like her every year.

Tags: , , ,

Category: Digital Pathology News, Education, Medical Research, Pathology News, Personal

Comments are closed.