Former Mayor Thomas Menino’s recently announced cancer diagnosis has many of us scratching our heads. How is it possible for a stealth cancer to spread to a person’s liver and lymph nodes without leaving a trace of where it originated?

About 31,000 cancer patients in the United States received a similar diagnosis last year, according to the American Cancer Society, representing fewer than 2 percent of all patients diagnosed with cancers. Despite all the tests and scans available today, doctors were unable to find a primary tumor.

“These cases are perplexing for several reasons,” said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. “Tumors generally show up in many places of the body at the same time, and they aren’t due to a previously missed diagnosis.” They’re also harder to treat because oncologists can’t pick from a list of chemotherapy drugs approved for a particular cancer.

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Broad-spectrum drugs that treat an array of cancers are typically chosen, but doctors don’t have the “level of certainty” they’d like when beginning treatment, Lichtenfeld said.

Menino began chemotherapy for the cancer detected in his liver and lymph nodes earlier this month at Dana-Farber Cancer Institute. His physicians there declined to comment on his treatment.

Menino’s primary care doctors at Brigham and Women’s Hospital told the Globe that they conducted an extensive search for the missing tumor to determine where the cancer originated via imaging scans and other medical tests, but they couldn’t find it and likely never will.

“It’s a very complicated process sometimes, and there isn’t one specific test we can do to determine the kind of cancer,” said Dr. Gauri Varadhachary, medical director of the gastrointestinal cancer center at MD Anderson Cancer Center in Dallas, who has not reviewed Menino’s medical records. Likely, she speculated, his doctors examined X-rays and images of the liver tumor to examine its anatomy, ran blood tests to screen for tumor markers or genetic mutations, and examined the malignant cells under the microscope to look for distinguishing features.

Pathologists frequently perform a special staining process called immunohistochemistry, or IHC, to look for specific proteins or receptors on cells that are hallmarks of certain cancers. Breast tumors, for example, sometimes have receptors for estrogen, progesterone or the growth factor HER2.

If all the initial tests are inconclusive, the tumor cells are likely to be labeled “unknown origin” and a primary source is only later found 2 to 3 percent of the time, Varadhachary told me.

What happened to the original tumor? Did it simply vanish? “We have a few hypotheses,” Varadhachary said, “but no clear proof from an animal model.” The initial cancer may be tiny—too small to detect on an imaging scan but aggressive enough to spread and proliferate abundantly throughout the body. It may also regress completely, destroyed by the body’s own immune system but too late to stop invading cancer cells that slipped undetected into the bloodstream.

While stealth cancers are uncommon and often just the result of bad luck, Menino had a host of health problems that predisposed him to cancer including type 2 diabetes, obesity, and two previous skin cancers, the common basal cell and squamous cell types that tend to be non-aggressive.

A study published last week found that people with previously diagnosed skin cancers—that weren’t the deadly melanoma type—were 36 percent more likely to be later diagnosed with a different kind of cancer than individuals who never had skin cancer.