MKSAP Quiz: 12-week history of night sweats, fevers, weight loss
A 33-year-old man is evaluated for a 12-week history of night sweats, fevers, and weight loss without other localizing symptoms. Medical history is otherwise unremarkable, and he takes no medications. Following a physical exam, lab tests, and other procedures, what is the most appropriate management?
A 33-year-old man is evaluated for a 12-week history of night sweats, fevers, and a 2.5-kg (5.6-lb) weight loss without other localizing symptoms. Medical history is otherwise unremarkable, and he takes no medications.
On thorough physical examination, temperature is 38.1 °C (100.6 °F); the remainder of vital signs are normal. Bilateral supraclavicular lymphadenopathy is noted. The examination is otherwise unremarkable.
Complete blood count, comprehensive metabolic profile, and serum α-fetoprotein and β-human chorionic gonadotropin levels are normal.
Testicular ultrasonography is normal. Contrast-enhanced CT scan of the chest, abdomen, and pelvis shows bulky retroperitoneal, mediastinal, and supraclavicular adenopathy.
An excisional biopsy of a supraclavicular node shows poorly differentiated carcinoma.
Which of the following is the most appropriate management?
A. Chemotherapy with a cisplatin-based germ cell regimen
B. Chemotherapy with a fluorouracil-based gastrointestinal cancer regimen
C. Stereotactic radiation therapy to involved lymph nodes
D. Surgical debulking of nodal disease
MKSAP Answer and Critique
The correct answer is A. Chemotherapy with a cisplatin-based germ cell regimen. This content is available to MKSAP 19 subscribers as Question 44 in the Oncology section. More information about MKSAP is available online.
The most appropriate management is chemotherapy with a cisplatin-based germ cell regimen (Option A). Despite steady improvements in diagnostic and imaging techniques during the past decades, a reasonable evaluation will not identify the source of cancer in a small number (less than 5%) of all patients presenting with metastatic cancer. This heterogeneous group of patients is classified as having cancer of unknown primary (CUP). Standard evaluation of CUP includes a full medical history and physical examination and contrast-enhanced CT of the chest, abdomen, and pelvis. Histologic evaluation of the most accessible tumor mass should include a limited number of immunohistochemical stains to assess the nature of the tumor and to identify or exclude treatable histologies (such as lymphoma or germ cell tumor). Ultimately, CUP is a diagnosis of exclusion after evaluation has failed to identify the primary tumor, which may either be too small to be detected or may have been destroyed immunologically and is no longer present. The patient is a young male with a poorly differentiated CUP that is predominantly presenting in a midline distribution. In the absence of a clearly identified primary, these patients should be treated presumptively for metastatic testicular (germ cell) cancer with a cisplatin-based chemotherapy regimen. The absence of serum α-fetoprotein and β-human chorionic gonadotropin, normal testicular examination, or even normal ultrasonography does not exclude this treatment approach.
A fluorouracil-based chemotherapy regimen (Option B) focused on digestive tract malignancies would be an appropriate consideration for an adenocarcinoma of unknown primary that was predominantly below the diaphragm with liver and/or peritoneal involvement.
The extent of disease described makes initial treatment with either surgery or radiation therapy (Options C, D) inappropriate, although these modalities might be considered for consolidation therapy at a later date if a good response to chemotherapy is obtained first.
Key Point
- Poorly differentiated carcinoma of unknown primary site that is predominantly presenting in a midline distribution should be treated presumptively for metastatic germ cell cancer with a cisplatin-based chemotherapy regimen.