Table 1. Tumor cell constellations with favorable prognosis. These affect about 20% to 30% of all patients with CUP syndrome and are treated with specific protocols.

Tumor constellation	Clinical presentation and recommended additional diagnostic procedures	Recommended therapy
Axillary lymph node metastases of an adenocarcinoma in women	Mammography, MRI and sonography of the breasts, possibly PET if available Immunohistology, including hormone receptor status and c-erbB2 expression	ESMO Minimal Clinical Recommendations: Therapy identical to the treatment of patients with mammary carcinoma and corresponding lymph node involvement (stage II)
Peritoneal carcinosis of a serous papillar adenocarcinoma in women	Tumor marker Ca 125 often increased Frequent in patients with BRCA1 mutations	ESMO Minimal Clinical Recommendations: Therapy identical to that of metastatic ovarian carcinoma in stage FIGO III
Cervical lymph node metastases of squamous cell carcinoma	CT and/or MRI of the neck; PET recommended ENT investigation with panendoscopy and biopsies of lesions If no suspicious lesions, ipsilateral tonsillectomy	General recommendation: Therapy as with metastatic ENT tumors with known primary tumors
Inguinal lymph node metastases of squamous cell carcinoma	Digital rectal investigation, proctoscopy Women: gynecological investigation with sample biopsies from lesions in the vulva, vagina and cervix	General recommendation: Lymph node dissection and /or local radiation lead to protracted remission in specific patients; possibly consider multimodal treatment concepts in analogy to anal, cervical or bladder carcinoma with combined radio-CHT
Undifferentiated neuroendocrine carcinoma	Determine degrees of differentiation and proliferation by histology Somatostatin receptor scintigraphy	General recommendation: Well differentiated, positive for somatostatin receptor: somatostatin Poorly differentiated: combination CHT with carboplatin/etoposide (level of evidence C)
Poorly differentiated carcinoma with germ cell characteristics	Young men (<50 years) with retroperitoneal and mediastinal lymph node metastases Beta-hCG and/or AFP often raised Cytogenetics: i(12p) aberration	General recommendation: In analogy to germ cell tumors, with combination CHT containing cisplatin, e.g. cisplatin/etoposide/bleomycin
Solitary metastasis	PET or PET-CT investigation Additional metastases are often diagnosed in hospital, so that curative therapy is rarely successful	General recommendation: Tumor resection and/or local radiation

AFP, alpha-fetoprotein; CHT, chemotherapy; beta-hCG, beta-human choriogonadotropin; PET, positron emission tomography; CT, computed tomography; ESMO, European Society of Medical Oncology; FIGO; Fédération Internationale de Gynécologie et Obstétrique