Case Presentation:

A 54‐year‐old woman presented to the ED with 6 months of right lower extremity swelling and intermittent pain. The swelling began after 3 international flights and had progressively worsened since. The pain was described as sharp, waxing with ambulation and waning with rest. Over the past 6 months, she had been diagnosed with cellulitis in the same leg and had a negative workup for deep venous thrombosis. Otherwise, her medical history was noncontributory. Her vital signs were within normal limits. The physical exam was remarkable for 3+ edema in the right lower extremity that extended from the foot to the right inguinal ligament. There was a palpable cord over the right greater saphenous vein and tenderness over the superficial femoral vein, but no erythema, hyperpigmentation, or increased varicosity. There was no palpable lymphadenopathy. Based on this exam, we proceeded with Doppler ultrasonography. We found a partial thrombus in the superficial femoral and deep saphenous veins as well as a 3 by 2 cm mass occluding the external iliac vein. Further imaging studies including CT and MRI did not provide additional information. A CT‐guided biopsy of this mass revealed squamous cell carcinoma. Pap smear, mammogram, proctoscopy, and skin exam were negative. CT of the chest, abdomen, and pelvis and a full‐body PET scan were negative for evidence of further disease. She is currently being treated with radiation and a planned resection. She is being followed closely as an outpatient.


Carcinoma of unknown primary origin accounts for at least 3% of all diagnosed cancers. Even with an extensive workup, the primary tumor goes undiagnosed in 20%–40% of cases. There are several proposed theories on how this occurs: (1) early metastasis before detection of the primary, (2) involution of the primary after metastasis because of an immunologic response, and (3) metastasis acquisition of proangiogenesis traits in which primary tumor growth is limited without those traits. In women, the initial workup for metastatic squamous cell carcinoma includes laboratory data, a careful Pap smear, a screening mammogram, and further investigation as guided by the results of these tests. As in our patient's case, it is also reasonable to obtain a CT as well as a PET scan if the primary is not identified after the initial investigations. Because squamous cell carcinoma tends to spread contiguously and lymphatically, all nearby tissues with squamous epithelium need to be explored. Because of the inguinal location in our patient, further investigation of the cervix and anus was absolutely necessary. Although advances in technology and pathologic techniques have significantly decreased the number of unknown primary cancers, they have not replaced the value of the hospitalist's diagnostic skill. An internist with sound methods and a thorough approach must still guide the patient through the appropriate workup for the best chance at a proper diagnosis.


See above.

Author Disclosure:

R. Beck, none; B. Rhodes, none; C. Miller, none.