Remembering Christine McVie: Understanding Cancer of Unknown Primary

What the record says

Christine McVie, the Fleetwood Mac singer and songwriter, died on November 30, 2022, at 79. Her family said she died in hospital after a short illness.

In April 2023 Rolling Stone reported details from her death certificate. The cause of death was an ischemic stroke, which happens when blood flow to part of the brain is cut off. The certificate also recorded "metastatic malignancy of unknown primary origin." E! News reported that atrial fibrillation, an irregular heart rhythm, was listed as a third contributing factor.

That is the whole public record, and this page does not go beyond it. What follows is what that phrase means.

Cancer without a return address

NCI defines cancer of unknown primary, or CUP, as a cancer confirmed by biopsy where no starting site can be found after the pathology and the scans are done.

Normally the starting point is obvious from the cells. Cancer that spreads keeps the look of the tissue it came from, not the place it lands. A tumor in the lung that is made of breast cells is breast cancer that moved. That is why doctors can usually name an origin even when they find the disease elsewhere first.

Sometimes the clues run out. NCI notes that in some people the primary site cannot be found even at autopsy.

Most CUP cases are adenocarcinoma, which starts in gland-like tissue, or undifferentiated tumors, whose cells are too disorganized to place. Less often the cells look like squamous carcinoma, melanoma, sarcoma, germ cell tumor, or a neuroendocrine tumor. Our page on cancer of unknown primary covers the same ground for people facing it now.

Rarer than it used to be

NCI states that with modern genomic profiling and PET-CT scanning, under 1% of new cancer diagnoses are now labeled CUP.

That figure is worth holding onto. The category is shrinking because the tools for finding origins keep improving, not because the disease changed.

How doctors hunt for the source

The pathologist leads. NCI describes a thorough look at an adequate tissue sample using histology, immunohistochemistry, which stains cells for proteins that mark their tissue of origin, molecular tests, next-generation sequencing, and sometimes electron microscopy.

Alongside that, NCI lists blood markers that can point somewhere: PSA for prostate, CA-125 for ovarian and other gynecologic cancers, CA 15-3 and CA 27.29 for breast, AFP and beta-hCG for germ cell tumors, and CEA, CA 19-9 or chromogranin A for other groups. MRI is added for head and neck, brain, pelvic, breast, prostate, or adrenal questions.

Where the disease has landed is itself a clue. NCI notes that lung metastases are twice as common when the origin turns out to sit above the diaphragm, while liver metastases point below it.

What treatment involves

NCI splits CUP into a favorable group and an unfavorable one.

Favorable means the pattern matches a known disease closely enough to borrow its playbook. NCI's examples include squamous cancer in neck nodes treated as head and neck cancer, adenocarcinoma in armpit nodes in a woman treated as breast cancer, bone-forming metastases treated on a breast or prostate model, raised AFP or beta-hCG treated as a germ cell tumor, and disease lining the abdomen treated as ovarian cancer. A single site of spread can sometimes be removed or irradiated.

The other route is molecular. The FDA has approved several targeted drugs for a genetic change regardless of where the cancer started. NCI lists high tumor mutational burden, high PD-L1, HER2, changes in NTRK, RET or EGFR, BRAF V600E, ROS1 fusions, MET amplification, and repair-deficiency or microsatellite instability.

Two randomized trials in 2019 tested whether gene expression profiling to guess the origin beat standard chemotherapy. It did not. Median progression-free survival was five months either way. A later meta-analysis of 1,114 people found the same. NCI notes those trials ran before most modern targeted drugs existed. Our page on metastatic cancer explains what spread means for treatment generally.

The outlook, stated honestly

NCI does not soften this. The prognosis for CUP is poor, and roughly 30% of people are alive at one year.

NCI lists what shifts the odds. Worse: adenocarcinoma or undifferentiated cells, disease outside the lymph nodes, older age, liver or adrenal involvement, being less well day to day, and a raised lactate dehydrogenase blood level. Better: disease confined to lymph nodes, neuroendocrine cells, a normal LDH, and being fully or nearly fully active.

These are group figures across a mixed set of diseases. They do not describe any one person, and NCI adds that molecular testing can find targets that change the picture substantially.

When to get checked

There is no screening test for CUP, and NCI has no evidence-based prevention advice for it. One risk factor is established: a review of nineteen studies found a clear increase in CUP risk with smoking.

Because CUP shows up as spread rather than a lump in one organ, the symptoms that matter are the general ones. None is specific to cancer. Each is worth a doctor's attention if it lasts more than two to three weeks:

• A swollen lymph node in the neck, armpit, or groin that is painless and not shrinking
• Weight loss you did not intend, especially 10% or more
• Bone pain in one spot that is worse at night
• A swollen abdomen, or new lasting abdominal pain
• A cough or breathlessness that will not settle

Routine screening matters here for a specific reason. It finds cancers while the origin is still obvious.

What this does not mean

• The reports describe a death certificate. They say nothing about her treatment, her stage, or what she knew, and this page does not infer any of it.
• "Unknown primary" does not mean untreatable. NCI sets out a favorable group whose care follows a known cancer's plan.
• The one-year figure is an average across a very mixed group. It is not a forecast for a person.
• A stroke recorded alongside cancer is not evidence that one caused the other. The certificate lists what was found, not a mechanism.

Sources

• Rolling Stone, Christine McVie Died of a Stroke and Metastasized Cancer — https://www.rollingstone.com/music/music-news/christine-mcvie-cause-of-death-stroke-cancer-1234709019/
• E! News, Fleetwood Mac Singer Christine McVie's Cause of Death Revealed — https://www.eonline.com/news/1370264/fleetwood-mac-singer-christine-mcvies-cause-of-death-revealed
• NCI, Carcinoma of Unknown Primary—Patient Version — https://www.cancer.gov/types/unknown-primary
• NCI PDQ, Cancer of Unknown Primary Treatment (Health Professional Version) — https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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